JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
Physical Activity Modifies the Associations between Genetic Variants and Blood Pressure in European Adolescents.
J. Pediatr.
PUBLISHED: 08-13-2014
Show Abstract
Hide Abstract
We hypothesized that physical activity and sedentary behavior could modify the associations between known genetic variants blood pressure-associated genes in European adolescents. Meeting current physical activity recommendations (?60 minutes/day) was able attenuate the deleterious effect of the NOS3 rs3918227 polymorphism on systolic blood pressure in European adolescents.
Related JoVE Video
Hypomethylation of the promoter of the catalytic subunit of protein phosphatase 2A in response to hyperglycemia.
Physiol Rep
PUBLISHED: 07-16-2014
Show Abstract
Hide Abstract
In order to identify epigenetic mechanisms through which hyperglycemia can affect gene expression durably in ? cells, we screened DNA methylation changes induced by high glucose concentrations (25 mmol/L) in the BTC3 murine cell line, using an epigenome-wide approach. Exposure of BTC3 cells to high glucose modified the expression of 1612 transcripts while inducing significant methylation changes in 173 regions. Among these 173 glucose-sensitive differentially methylated regions (DMRs), 14 were associated with changes in gene expression, suggesting an epigenetic effect of high glucose on gene transcription at these loci. Among these 14 DMRs, we selected for further study Pp2ac, a gene previously suspected to play a role in ?-cell physiology and type 2 diabetes. Using RT-qPCR and bisulfite pyrosequencing, we confirmed our previous observations in BTC3 cells and found that this gene was significantly demethylated in the whole blood cells (WBCs) of type 2 diabetic patients compared to controls.
Related JoVE Video
Associations of early life and sociodemographic factors with menarcheal age in European adolescents.
Eur. J. Pediatr.
PUBLISHED: 04-01-2014
Show Abstract
Hide Abstract
Early menarche has been associated with adult overweight, cardiovascular risk factors, and other diseases. Little is known about the determinants of menarcheal age (MA). Therefore, the main aim of this study was to examine the associations between early life programming factors and menarcheal age in European adolescents. Secondly, the influence of sociodemographical factors on menarcheal age was also studied. A total of 1,069 European girls from the HELENA cross-sectional study, aged 12.5-17.5 years, were included in this study. Using multilevel linear regression models, a possible association between birth weight and length, ponderal index at birth, gestational age, duration of exclusive breastfeeding, and menarcheal age was examined. Associations between geographical gradient, number of siblings, physical activity (PA), dietary factors, and menarcheal age were also examined. After adjustment, menarcheal age was positively associated with birth weight and length (p?=?0.01 and p?=?0.01). Conclusion: These findings confirm that birth weight and length may have a programming effect on menarcheal age. Next to this finding, sociodemographic factors were not associated with menarcheal age.
Related JoVE Video
Effects of established BMI-associated loci on obesity-related traits in a French representative population sample.
BMC Genet.
PUBLISHED: 01-14-2014
Show Abstract
Hide Abstract
Genome-wide association studies have identified variants associated with obesity-related traits, such as the body mass index (BMI). We sought to determine how the combination of 31 validated, BMI-associated loci contributes to obesity- and diabetes-related traits in a French population sample. The MONA LISA Lille study (1578 participants, aged 35-74) constitutes a representative sample of the population living in Lille (northern France). Genetic variants were considered both individually and combined into a genetic predisposition score (GPS).
Related JoVE Video
Associations of genetic variants in/near body mass index-associated genes with type 2 diabetes: a systematic meta-analysis.
Clin. Endocrinol. (Oxf)
PUBLISHED: 01-12-2014
Show Abstract
Hide Abstract
Genome-wide association studies have identified many obesity/body mass index (BMI)-associated loci in Europeans and East Asians. Since then, a large number of studies have investigated the role of BMI-associated loci in the development of type 2 diabetes (T2D). However, the results have been inconsistent. The objective of this study was to investigate the associations of eleven obesity/BMI loci with T2D risk and explore how BMI influences this risk.
Related JoVE Video
Impact of APOE gene polymorphisms on the lipid profile in an Algerian population.
Lipids Health Dis
PUBLISHED: 08-27-2013
Show Abstract
Hide Abstract
The importance of apolipoprotein E (APOE) in lipid and lipoprotein metabolism is well established. However, the impact of APOE polymorphisms has never been investigated in an Algerian population. This study assessed, for the fist time, the relationships between three APOE polymorphisms (epsilon, rs439401, rs4420638) and plasma lipid concentrations in a general population sample from Algeria.
Related JoVE Video
CD36 and SR-BI are involved in cellular uptake of provitamin A carotenoids by Caco-2 and HEK cells, and some of their genetic variants are associated with plasma concentrations of these micronutrients in humans.
J. Nutr.
PUBLISHED: 02-20-2013
Show Abstract
Hide Abstract
Scavenger receptor class B type I (SR-BI) and cluster determinant 36 (CD36) have been involved in cellular uptake of some provitamin A carotenoids. However, data are incomplete (e.g., there are no data on ?-carotene), and it is not known whether genetic variants in their encoding genes can affect provitamin A carotenoid status. The objectives were 1) to assess the involvement of these scavenger receptors in cellular uptake of the main provitamin A carotenoids (i.e., ?-carotene, ?-carotene, and ?-cryptoxanthin) as well as that of preformed vitamin A (i.e., retinol) and 2) to investigate the contribution of genetic variations in genes encoding these proteins to interindividual variations in plasma concentrations of provitamin A carotenoids. The involvement of SR-BI and CD36 in carotenoids and retinol cellular uptake was investigated in Caco-2 and human embryonic kidney (HEK) cell lines. The involvement of scavenger receptor class B type I (SCARB1) and CD36 genetic variants on plasma concentrations of provitamin A carotenoids was assessed by association studies in 3 independent populations. Cell experiments suggested the involvement of both proteins in cellular uptake of provitamin A carotenoids but not in that of retinol. Association studies showed that several plasma provitamin A carotenoid concentrations were significantly different (P < 0.0083) between participants who bore different genotypes at single nucleotide polymorphisms and haplotypes in CD36 and SCARB1. In conclusion, SR-BI and CD36 are involved in cellular uptake of provitamin A carotenoids, and genetic variations in their encoding genes may modulate plasma concentrations of provitamin A carotenoids at a population level.
Related JoVE Video
Body size at birth modifies the effect of fat mass and obesity associated (FTO) rs9939609 polymorphism on adiposity in adolescents: the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study.
Br. J. Nutr.
PUBLISHED: 09-15-2011
Show Abstract
Hide Abstract
The present study was intended to examine whether ponderal index (PI) at birth modifies the effect of the fat mass and obesity associated (FTO) rs9939609 polymorphism on adiposity in European adolescents. A total of 628 adolescents aged 14·4 (se 1·3) years (56·8 % female) were recruited. PI was calculated from parental reports of birth weight and length (kg/m³), and the BMI (kg/m²), body fat percentage and fat mass index (FMI, kg/m²) were calculated. The rs9939609 polymorphism was genotyped and physical activity assessed by accelerometry. Sex, duration of pregnancy, pubertal status, centre and physical activity were used as confounders in all the analyses. The minor A allele of the FTO rs9939609 was significantly associated with higher BMI, body fat percentage and FMI (all P < 0·05) but not with PI. Significant interactions between PI and the rs9939609 polymorphism in terms of body fat percentage (P = 0·002) and FMI (P = 0·017) were detected. However, this polymorphism was only significantly associated with higher BMI, body fat percentage and FMI (all P < 0·05) in adolescents in the lower PI tertile. Indeed, both body fat percentage and FMI were higher in those adolescents in the lower PI tertile carrying the A allele of the FTO rs9939609 polymorphism than in those with the TT genotype (25·0 (se 0·8) v. 22·1 (se 1·0) %, adjusted P = 0·030 and 5·6 (se 0·3) v. 4·6 (se 0·4) kg/m2, P = 0·031, respectively). Our findings suggest that those adolescents born with lower PI could be more vulnerable to the influence of the A risk allele of the FTO polymorphism on total adiposity content.
Related JoVE Video
Association between a thyroid hormone receptor-? gene polymorphism and blood pressure but not with coronary heart disease risk.
Am. J. Hypertens.
PUBLISHED: 06-09-2011
Show Abstract
Hide Abstract
Thyroid hormones (THs) exert multiple biological roles including effects on the cardiovascular system (lipid profile, blood pressure (BP) and cardiac output). The lipid-lowering actions of TH are mediated by the TH receptor-? whereas the mechanisms explaining the BP variations concomitant with the thyroid disorders are less understood. As the TH receptor-? (TR-?) has been associated with many of TH actions on the cardiovascular system in mice models, we hypothesized that it could be involved in the latter. We thus tested whether polymorphisms in TR-? (THRA gene) could be associated with BP level variation. Secondarily, we tested for association with coronary heart disease (CHD) risk.
Related JoVE Video
FADS1 genetic variability interacts with dietary ?-linolenic acid intake to affect serum non-HDL-cholesterol concentrations in European adolescents.
J. Nutr.
PUBLISHED: 05-18-2011
Show Abstract
Hide Abstract
Two rate-limiting enzymes in PUFA biosynthesis, ?5- and ?6-desaturases, are encoded by the FADS1 and FADS2 genes, respectively. Genetic variants in the FADS1-FADS2 gene cluster are associated with changes in plasma concentrations of PUFA, HDL- and LDL-cholesterol, and TG. However, little is known about whether dietary PUFA intake modulates these associations, especially in adolescents. We assessed whether dietary linoleic acid (LA) or ?-linolenic acid (ALA) modulate the association between the FADS1 rs174546 polymorphism and concentrations of PUFA, other lipids, and lipoproteins in adolescents. Dietary intakes of LA and ALA, FADS1 rs174546 genotypes, PUFA levels in serum phospholipids, and serum concentrations of TG, cholesterol, and lipoproteins were determined in 573 European adolescents from the HELENA study. The sample was stratified according to the median dietary LA (?9.4 and >9.4 g/d) and ALA (?1.4 and >1.4 g/d) intakes. The associations between FADS1 rs174546 and concentrations of PUFA, TG, cholesterol, and lipoproteins were not affected by dietary LA intake (all P-interaction > 0.05). Similarly, the association between the FADS1 rs174546 polymorphism and serum phospholipid concentrations of ALA or EPA was not modified by dietary ALA intake (all P-interaction > 0.05). In contrast, the rs174546 minor allele was associated with lower total cholesterol concentrations (P = 0.01 under the dominant model) and non-HDL-cholesterol concentrations (P = 0.02 under the dominant model) in the high-ALA-intake group but not in the low-ALA-intake group (P-interaction = 0.01). These results suggest that dietary ALA intake modulates the association between FADS1 rs174546 and serum total and non-HDL-cholesterol concentrations at a young age.
Related JoVE Video
Physical activity attenuates the influence of FTO variants on obesity risk: a meta-analysis of 218,166 adults and 19,268 children.
Tuomas O Kilpeläinen, Lu Qi, Soren Brage, Stephen J Sharp, Emily Sonestedt, Ellen Demerath, Tariq Ahmad, Samia Mora, Marika Kaakinen, Camilla Helene Sandholt, Christina Holzapfel, Christine S Autenrieth, Elina Hyppönen, Stéphane Cauchi, Meian He, Zoltan Kutalik, Meena Kumari, Alena Stančáková, Karina Meidtner, Beverley Balkau, Jonathan T Tan, Massimo Mangino, Nicholas J Timpson, Yiqing Song, M Carola Zillikens, Kathleen A Jablonski, Melissa E Garcia, Stefan Johansson, Jennifer L Bragg-Gresham, Ying Wu, Jana V van Vliet-Ostaptchouk, N Charlotte Onland-Moret, Esther Zimmermann, Natalia V Rivera, Toshiko Tanaka, Heather M Stringham, Günther Silbernagel, Stavroula Kanoni, Mary F Feitosa, Soren Snitker, Jonatan R Ruiz, Jeffery Metter, Maria Teresa Martinez Larrad, Mustafa Atalay, Maarit Hakanen, Najaf Amin, Christine Cavalcanti-Proença, Anders Grøntved, Göran Hallmans, John-Olov Jansson, Johanna Kuusisto, Mika Kähönen, Pamela L Lutsey, John J Nolan, Luigi Palla, Oluf Pedersen, Louis Pérusse, Frida Renstrom, Robert A Scott, Dmitry Shungin, Ulla Sovio, Tuija H Tammelin, Tapani Rönnemaa, Timo A Lakka, Matti Uusitupa, Manuel Serrano Rios, Luigi Ferrucci, Claude Bouchard, Aline Meirhaeghe, Mao Fu, Mark Walker, Ingrid B Borecki, George V Dedoussis, Andreas Fritsche, Claes Ohlsson, Michael Boehnke, Stefania Bandinelli, Cornelia M van Duijn, Shah Ebrahim, Debbie A Lawlor, Vilmundur Gudnason, Tamara B Harris, Thorkild I A Sørensen, Karen L Mohlke, Albert Hofman, André G Uitterlinden, Jaakko Tuomilehto, Terho Lehtimäki, Olli Raitakari, Bo Isomaa, Pål R Njølstad, Jose C Florez, Simin Liu, Andy Ness, Timothy D Spector, E Shyong Tai, Philippe Froguel, Heiner Boeing, Markku Laakso, Michael Marmot, Sven Bergmann, Chris Power, Kay-Tee Khaw, Daniel Chasman, Paul Ridker, Torben Hansen, Keri L Monda, Thomas Illig, Marjo-Riitta Järvelin, Nicholas J Wareham, Frank B Hu, Leif C Groop, Marju Orho-Melander, Ulf Ekelund, Paul W Franks, Ruth J F Loos.
PLoS Med.
PUBLISHED: 04-21-2011
Show Abstract
Hide Abstract
The FTO gene harbors the strongest known susceptibility locus for obesity. While many individual studies have suggested that physical activity (PA) may attenuate the effect of FTO on obesity risk, other studies have not been able to confirm this interaction. To confirm or refute unambiguously whether PA attenuates the association of FTO with obesity risk, we meta-analyzed data from 45 studies of adults (n?=?218,166) and nine studies of children and adolescents (n?=?19,268).
Related JoVE Video
The effect of ponderal index at birth on the relationships between common LEP and LEPR polymorphisms and adiposity in adolescents.
Obesity (Silver Spring)
PUBLISHED: 04-21-2011
Show Abstract
Hide Abstract
This study examined the effect of ponderal index (PI) at birth on the relationships between eight common polymorphisms of the leptin (LEP) and leptin receptor (LEPR) genes and adiposity in adolescents. A total of 823 European adolescents (45.4% girls) aged 14.8 ± 1.4 years were genotyped for the LEP (rs2167270, rs12706832, rs10244329, rs2071045, and rs3828942) and LEPR (rs1137100, rs1137101, and rs8179183) polymorphisms. The PI was calculated from parental reports of birth weight and length. Fat mass index (FMI) was calculated. Analyses were adjusted for relevant confounders. An "adiposity-risk-allele score" based on genotypes at the three single-nucleotide polymorphisms (SNPs) associated with adolescents FMI in adolescents within the lower tertile of PI was calculated. The LEP rs10244329 and rs3828942 polymorphisms were associated with higher FMI only in adolescents within the lower PI tertile (+0.55 kg/m(2) per minor T allele, P = 0.040, and +0.58 kg/m(2) per major G allele, P = 0.028, respectively). The LEPR rs8179183 polymorphism was significantly associated with higher FMI in adolescents within the lower PI tertile (+0.87 kg/m(2) per minor C allele, P = 0.006). After correction for multiple comparisons, only the association between the LEPR rs8179183 and FMI persisted. However, each additional risk allele conferred 0.53 kg/m(2) greater FMI in adolescents within the lower tertile of PI (P = 0.008). In conclusion, our results suggest that those adolescents born with lower PI could be more vulnerable to the influence of the LEP rs10244329 and rs3828942 polymorphisms and LEPR rs8179183 polymorphism on total adiposity content. Due to the relatively small sample size, these findings should be replicated in further larger population samples.
Related JoVE Video
Mendelian randomization study of B-type natriuretic peptide and type 2 diabetes: evidence of causal association from population studies.
PLoS Med.
PUBLISHED: 03-13-2011
Show Abstract
Hide Abstract
Genetic and epidemiological evidence suggests an inverse association between B-type natriuretic peptide (BNP) levels in blood and risk of type 2 diabetes (T2D), but the prospective association of BNP with T2D is uncertain, and it is unclear whether the association is confounded.
Related JoVE Video
Polymorphisms in the CD36/FAT gene are associated with plasma vitamin E concentrations in humans.
Am. J. Clin. Nutr.
PUBLISHED: 01-12-2011
Show Abstract
Hide Abstract
Blood vitamin E concentrations are modulated by dietary, metabolic, and genetic factors. CD36 (cluster of differentiation 36), a class B scavenger receptor, might be involved in tissue vitamin E uptake and thus would influence blood vitamin E concentrations.
Related JoVE Video
Associations between common genetic polymorphisms in the liver X receptor alpha and its target genes with the serum HDL-cholesterol concentration in adolescents of the HELENA Study.
Atherosclerosis
PUBLISHED: 01-03-2011
Show Abstract
Hide Abstract
Genetic variability in the NR1H3 gene (encoding LXR?) and in several of its target genes is associated with serum HDL-cholesterol (HDL-C) concentrations. We sought to assess if these associations could be detected in adolescents.
Related JoVE Video
Common polymorphisms in six genes of the methyl group metabolism pathway and obesity in European adolescents.
Int J Pediatr Obes
PUBLISHED: 10-01-2010
Show Abstract
Hide Abstract
The goal of the present study was to assess the relationship between the genetic variability in six genes of methyl group (CH(3)) metabolism and the risk of obesity.
Related JoVE Video
Suggestive evidence of associations between liver X receptor ? polymorphisms with type 2 diabetes mellitus and obesity in three cohort studies: HUNT2 (Norway), MONICA (France) and HELENA (Europe).
BMC Med. Genet.
PUBLISHED: 05-11-2010
Show Abstract
Hide Abstract
The liver X receptors (LXR) ? and ? regulate lipid and carbohydrate homeostasis and inflammation. Lxr??/? mice are glucose intolerant and at the same time lean. We aimed to assess the associations between single nucleotide polymorphisms (SNPs) in LXR? and risk of type 2 diabetes mellitus (T2DM), obesity and related traits in 3 separate cohort studies.
Related JoVE Video
No association between polymorphisms in the INSIG1 gene and the risk of type 2 diabetes and related traits.
Am. J. Clin. Nutr.
PUBLISHED: 05-05-2010
Show Abstract
Hide Abstract
The insulin-induced gene 1 (INSIG1) encodes a protein that blocks proteolytic activation of sterol regulatory element binding proteins, which are transcription factors that activate genes that regulate cholesterol, fatty acid, and glucose metabolism.
Related JoVE Video
Single nucleotide polymorphisms in the FADS gene cluster are associated with delta-5 and delta-6 desaturase activities estimated by serum fatty acid ratios.
J. Lipid Res.
PUBLISHED: 04-28-2010
Show Abstract
Hide Abstract
Genetic variability in the FADS1-FADS2 gene cluster [encoding delta-5 (D5D) and delta-6 (D6D) desaturases] has been associated with plasma long-chain PUFA (LCPUFA) and lipid levels in adults. To better understand these relationships, we further characterized the association between FADS1-FADS2 genetic variability and D5D and D6D activities in adolescents. Thirteen single nucleotide polymorphisms (SNPs) were genotyped in 1,144 European adolescents (mean +/- SD age: 14.7 +/- 1.4 y). Serum phospholipid fatty acid levels were analyzed using gas chromatography. D5D and D6D activities were estimated from the C20:4n-6/C20:3n-6 and C20:3n-6/C18:2n-6 ratios, respectively. Minor alleles of nine SNPs were associated with higher 18:2n-6 levels (1.9E-18
Related JoVE Video
Concordance of two multiple analytical approaches demonstrate that interaction between BMI and ADIPOQ haplotypes is a determinant of LDL cholesterol in a general French population.
J. Hum. Genet.
PUBLISHED: 02-26-2010
Show Abstract
Hide Abstract
Genetic and environmental factors are involved in insulin resistance (IR). IR and dyslipidemia associate with increased risk of cardiovascular diseases. Plasma low-density lipoprotein cholesterol (LDL-C) level is a marker of cardiovascular risk. In a Caucasian general population we aimed at determining the multifactorial components of LDL-C levels using 10 genes and 3 phenotypes. In the PPARG, UCP3, ADIPOQ, TNF, LIPC, CARTPT, PCSK9, SCAP, SCARB1 and ENPP1 genes known to be associated with IR or dyslipidemia we genotyped 19 single nucleotide polymorphisms (SNPs) in 846 subjects. When several SNPs were genotyped for a given gene we constructed haplotypes. Including genetic and environmental variables (gender, body mass index (BMI) and adiponectin level) we used (1) the multifactor dimensionality reduction method to explain clusters of high and low LDL-C, and (2) the restricted partition method to explain LDL-C levels. Both methods showed that BMI and haplotypes at the ADIPOQ adiponectin encoding gene but not adiponectin level itself, were discriminant regarding to LDL-C. Subjects bearing an at-risk combination of BMI and ADIPOQ genotypes were prone to have a higher LDL-C (OR=3.13, 95% CI=2.20-4.46, P<0.0001). Our results suggest that in interaction with BMI, ADIPOQ haplotypes capture genetic variation(s) from neighboring gene(s) that would modulate LDL-C level.
Related JoVE Video
Single-nucleotide polymorphism of CD36 locus and obesity in European adolescents.
Obesity (Silver Spring)
PUBLISHED: 11-05-2009
Show Abstract
Hide Abstract
CD36 is a membrane receptor with a wide variety of functions, including the regulation of energy metabolism, fat storage, and adipocyte differentiation. To assess the relationship between CD36 gene single-nucleotide polymorphisms (SNPs) and obesity in adolescents, we evaluated the relationship between CD36 SNPs and the risk of obesity in a case-control study composed of 307 obese (age = 15.0 +/- 1.1 years) and 339 normal-weight adolescents (age = 14.6 +/- 1.1 years). To validate the results, we assessed the relation between the same SNPs and percentage of body fat (BF%) and BMI in 1,151 European adolescents (age = 14.8 +/- 1.4 years). SNPs with a minor allele frequency >0.10 were selected to tag CD36. Genotyping was performed on an Illumina system. Four SNPs (rs3211867, rs3211883, rs3211908, and rs1527483) were associated with increased risk of obesity in the case-control study (odds ratio (OR) (95% confidence interval)): 1.96 (1.26-3.04], P = 0.003; 1.73 (1.16-2.59), P = 0.007; 2.42 (1.47-4.01), P = 0.0005 and 1.95 (1.25-3.05), P = 0.003, respectively). The same four SNPs were associated with higher BMI (P < 0.05) and BF% (P < 0.04) in the validation study. Further analyses identified a haplotype (frequency: 0.05) carrying the minor allele of these SNPs as being associated with obesity (OR: 2.28; P = 0.0008) in the case-control study and with excess adiposity (i.e., higher BF% (P = 0.03) and BMI (P = 0.04)) in the validation study. Our data suggest that genetic variability at the CD36 gene locus could be associated with body weight variability in European adolescents but these findings require replication.
Related JoVE Video
Associations between common genetic polymorphisms in angiopoietin-like proteins 3 and 4 and lipid metabolism and adiposity in European adolescents and adults.
J. Clin. Endocrinol. Metab.
PUBLISHED: 11-04-2009
Show Abstract
Hide Abstract
Plasma-borne angiopoietin-like proteins (ANGPTL) act as endocrine factors on their target tissues. Because ANGPTL3 and ANGPTL4 play important roles in lipid metabolism and the regulation of adiposity in mice, we hypothesized that genetic variability at the ANGPTL3 and ANGPTL4 genes loci might influence lipid metabolism and fat deposition in humans.
Related JoVE Video
Breast-feeding modulates the influence of the peroxisome proliferator-activated receptor-gamma (PPARG2) Pro12Ala polymorphism on adiposity in adolescents: The Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) cross-sectional study.
Diabetes Care
PUBLISHED: 10-21-2009
Show Abstract
Hide Abstract
The peroxisome proliferator-activated receptor-gamma2 (PPARG2) Pro12Ala polymorphism has been associated with a higher BMI and a lower risk of type 2 diabetes in adulthood. The association between adiposity and PPARG variants can be influenced by environmental factors such as early growth, dietary fat, and (as recently shown) breast-feeding. The objectives of this study were to assess 1) the influence of the PPARG2 Pro12Ala polymorphism on adiposity markers in adolescents and 2) a possible modulating effect of breast-feeding on these associations.
Related JoVE Video
Related JoVE Video
Peroxisome proliferator-activated receptor gamma polymorphisms and coronary heart disease.
PPAR Res
PUBLISHED: 06-11-2009
Show Abstract
Hide Abstract
Single nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptor gamma (PPARG) gene have been associated with cardiovascular risk factors, particularly obesity and diabetes. We assessed the relationship between 4 PPARG SNPs (C-681G, C-689T, Pro12Ala, and C1431T) and coronary heart disease (CHD) in the PRIME (249 cases/494 controls, only men) and ADVANCE (1,076 cases/805 controls, men or women) studies. In PRIME, homozygote individuals for the minor allele of the PPARG C-689T, Pro12Ala, and C1431T SNPs tended to have a higher risk of CHD than homozygote individuals for the frequent allele (adjusted OR [95% CI] = 3.43 [0.96-12.27], P = .058, 3.41 [0.95-12.22], P = .060 and 5.10 [0.99-26.37], P = .050, resp.). No such association could be detected in ADVANCE. Haplotype distributions were similar in cases and control in both studies. A meta-analysis on the Pro12Ala SNP, based on our data and 11 other published association studies (6,898 CHD cases/11,287 controls), revealed that there was no evidence for a significant association under the dominant model (OR = 0.99 [0.92-1.07], P = .82). However, there was a borderline association under the recessive model (OR = 1.29 [0.99-1.67], P = .06) that became significant when considering men only (OR = 1.73 [1.20-2.48], P = .003). In conclusion, the PPARG Ala12Ala genotype might be associated with a higher CHD risk in men but further confirmation studies are needed.
Related JoVE Video
In obese and non-obese adults, the cis-regulatory rs361072 promoter variant of PIK3CB is associated with insulin resistance not with type 2 diabetes.
Mol. Genet. Metab.
PUBLISHED: 03-21-2009
Show Abstract
Hide Abstract
We recently reported that rs361072, a promoter C/T variant of p110beta, the catalytic subunit of PI3-kinase, was associated with a protection from insulin resistance (IR) in Caucasian adolescents in proportion of their body mass. We tested if this cis-regulatory QTL is associated with IR and type 2 diabetes in 7885 middle-aged obese and non-obese adults of European ancestry. We genotyped rs361072 in 1139 non-diabetic obese (NDO) European adults, in whom IR was estimated by the HOMA-IR index. We also studied 427 type 2 diabetic obese adults (DO) and 424 diabetic non-obese (DNO) adults to test whether their disease status was associated with a decreased prevalence of the protective variant. The prevalence of rs361072 and association with IR was also examined in 5895 non-obese non-diabetic adults (NDNO). rs361072 was associated with HOMA-IR (p=4.10(-4)) in NDO, so that C/C patients had a 17% decrease of this index (p=0.002). A statistical trend (p=1.1.10(-2)) for the same genotypic differences was also observed in NDNO adults, but of insignificant magnitude (4.2%). The distribution of rs361072 genotype was comparable in NDO, DO, DNO and NDNO individuals. Allele C of rs361072 is associated with a protection from IR in obese and non-obese adults, but has no significant effect, however, on diabetes risk in obese or non-obese Europeans.
Related JoVE Video
Effect of an FTO polymorphism on fat mass, obesity, and type 2 diabetes mellitus in the French MONICA Study.
Metab. Clin. Exp.
PUBLISHED: 02-09-2009
Show Abstract
Hide Abstract
We investigated the association between the rs9939609 (T>A) polymorphism in the FTO (fat mass- and obesity-associated) gene and obesity- and type 2 diabetes mellitus-related phenotypes in the French Multinational MONItoring of Trends and Determinants in CArdiovascular Disease (MONICA) Study (n = 3367). In the study, TA or AA subjects had higher body mass index (BMI) (P = .017), waist circumference (P = .017), and hip (P = .01) circumference in an A allele dose-dependent manner. The A allele was also significantly associated with higher plasma insulin levels (P = .05), higher insulin resistance index (homeostasis model assessment) (P = .02), and higher systolic blood pressure (P = .003); but these associations disappeared after adjustment for BMI. In the study, 598 subjects were obese (BMI >or=30 kg/m(2)); and 2769 subjects were not obese (BMI <30 kg/m(2)). Subjects bearing the A allele of rs9939609 had a higher risk of obesity (adjusted odds ratio [95% confidence interval] = 1.29 [1.06-1.58], P = .01) compared with TT subjects. Moreover, the homozygous AA genotype of rs9939609 was associated with a higher risk of type 2 diabetes mellitus (odds ratio = 1.45 [1.05-1.99], P = .02, 283 subjects with and 2601 subjects without type 2 diabetes mellitus), independently of BMI. In conclusion, the role of the A allele of the FTO rs9939609 polymorphism on the risk of obesity and type 2 diabetes mellitus was confirmed in the French MONICA Study.
Related JoVE Video
Study of the genetic variability of ZAC1 (PLAGL1) in French population-based samples.
J. Hypertens.
PUBLISHED: 01-22-2009
Show Abstract
Hide Abstract
ZAC1 (zinc finger protein regulating apoptosis and cell cycle arrest) is a member of the new subfamily of zinc-finger transcription factors, designated as PLAG (pleomorphic adenoma gene) family. The ZAC1 gene is maternally imprinted and is linked to developmental disorders such as growth retardation and transient neonatal diabetes mellitus. We wanted to assess whether the genetic variability of the ZAC1 gene was associated with anthropometric (weight, BMI, waist-to-hip ratio) or biochemical (plasma lipid, insulin, glucose levels, blood pressure level) phenotypes.
Related JoVE Video
Study of thyroid hormone receptor alpha gene polymorphisms on Alzheimers disease.
Neurobiol. Aging
PUBLISHED: 01-09-2009
Show Abstract
Hide Abstract
Because the action of thyroid hormone (T3) is involved in adult cognitive functions, we wanted to assess the association between THRA gene polymorphisms, which encodes the T3 nuclear receptor TR?1, and Alzheimers disease (AD) risk. We analysed 5 single nucleotide polymorphisms (SNPs) of THRA, covering the known common genetic variability of the gene, in the Lille AD case-control study (710 cases/597 controls). We observed that subjects bearing the rs939348 TT genotype had a tendency to have a higher risk of developing AD (adjusted OR [95%CI]=1.71 [0.99-2.95] p=0.06). We extended our finding to three other independent AD case-control studies and observed similar trends. When combining the 4 studies (1749 cases/1339 controls), we observed an overall significant higher risk of AD in TT subjects (adjusted OR [95%CI]=1.42 [1.03-1.96], p=0.03) compared with C allele bearers. However, when combining our data with the available data coming from 2 American genome wide association studies on AD, we observed a weak and not significant association (OR=1.19 [0.97-1.45], p=0.10). The relationship between the genetic variability of the THRA gene and AD risk remains uncertain but cannot be entirely excluded.
Related JoVE Video
Genetic and molecular insights into the role of PROX1 in glucose metabolism.
Diabetes
Show Abstract
Hide Abstract
Genome-wide association studies have shown that the rs340874 single nucleotide polymorphism (SNP) in PROX1 is a genetic susceptibility factor for type 2 diabetes. We conducted genetic and molecular studies to better understand the role of PROX1 in type 2 diabetes. We assessed the impact of the whole common genetic variability of PROX1 (80 SNPs) on type 2 diabetes-related biochemical traits in the HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence) study (n = 1,155). Three SNPs (rs340838, rs340837, and rs340836) were significantly associated with fasting plasma insulin levels (P ? 0.00295). We evaluated the impact of nine PROX1 SNPs (the three insulin-associated SNPs plus six SNPs in strong linkage disequilibrium) on luciferase reporter gene expression. The insulin-lowering alleles of rs340874, rs340873, and rs340835 were associated with lower luciferase activity in MIN6 and HepG2 cells (except for rs340874, which was in HepG2 cells only). Electrophoretic mobility shift assays indicated that specific nuclear protein bindings occur at the three SNPs in HepG2 cells, with allele-binding differences for rs340874. We also showed that the knockdown of Prox1 expression by small interfering RNAs in INS-1E cells resulted in a 1.7-fold reduction in glucose-stimulated insulin secretion. All together, we propose that reduced expression of PROX1 by cis-regulatory variants results in altered ?-cell insulin secretion and thereby confers susceptibility to type 2 diabetes.
Related JoVE Video
New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism.
Momoko Horikoshi, Hanieh Yaghootkar, Dennis O Mook-Kanamori, Ulla Sovio, H Rob Taal, Branwen J Hennig, Jonathan P Bradfield, Beate St Pourcain, David M Evans, Pimphen Charoen, Marika Kaakinen, Diana L Cousminer, Terho Lehtimäki, Eskil Kreiner-Møller, Nicole M Warrington, Mariona Bustamante, Bjarke Feenstra, Diane J Berry, Elisabeth Thiering, Thiemo Pfab, Sheila J Barton, Beverley M Shields, Marjan Kerkhof, Elisabeth M van Leeuwen, Anthony J Fulford, Zoltan Kutalik, Jing Hua Zhao, Marcel den Hoed, Anubha Mahajan, Virpi Lindi, Liang-Kee Goh, Jouke-Jan Hottenga, Ying Wu, Olli T Raitakari, Marie N Harder, Aline Meirhaeghe, Ioanna Ntalla, Rany M Salem, Karen A Jameson, Kaixin Zhou, Dorota M Monies, Vasiliki Lagou, Mirna Kirin, Jani Heikkinen, Linda S Adair, Fowzan S Alkuraya, Ali Al-Odaib, Philippe Amouyel, Ehm Astrid Andersson, Amanda J Bennett, Alexandra I F Blakemore, Jessica L Buxton, Jean Dallongeville, Shikta Das, Eco J C de Geus, Xavier Estivill, Claudia Flexeder, Philippe Froguel, Frank Geller, Keith M Godfrey, Frederic Gottrand, Christopher J Groves, Torben Hansen, Joel N Hirschhorn, Albert Hofman, Mads V Hollegaard, David M Hougaard, Elina Hyppönen, Hazel M Inskip, Aaron Isaacs, Torben Jørgensen, Christina Kanaka-Gantenbein, John P Kemp, Wieland Kiess, Tuomas O Kilpeläinen, Norman Klopp, Bridget A Knight, Christopher W Kuzawa, George McMahon, John P Newnham, Harri Niinikoski, Ben A Oostra, Louise Pedersen, Dirkje S Postma, Susan M Ring, Fernando Rivadeneira, Neil R Robertson, Sylvain Sebert, Olli Simell, Torsten Slowinski, Carla M T Tiesler, Anke Tönjes, Allan Vaag, Jorma S Viikari, Jacqueline M Vink, Nadja Hawwa Vissing, Nicholas J Wareham, Gonneke Willemsen, Daniel R Witte, Haitao Zhang, Jianhua Zhao, , James F Wilson, Michael Stumvoll, Andrew M Prentice, Brian F Meyer, Ewan R Pearson, Colin A G Boreham, Cyrus Cooper, Matthew W Gillman, George V Dedoussis, Luis A Moreno, Oluf Pedersen, Maiju Saarinen, Karen L Mohlke, Dorret I Boomsma, Seang-Mei Saw, Timo A Lakka, Antje Körner, Ruth J F Loos, Ken K Ong, Peter Vollenweider, Cornelia M van Duijn, Gerard H Koppelman, Andrew T Hattersley, John W Holloway, Berthold Hocher, Joachim Heinrich, Chris Power, Mads Melbye, Mònica Guxens, Craig E Pennell, Klaus Bønnelykke, Hans Bisgaard, Johan G Eriksson, Elisabeth Widén, Hakon Hakonarson, André G Uitterlinden, Anneli Pouta, Debbie A Lawlor, George Davey Smith, Timothy M Frayling, Mark I McCarthy, Struan F A Grant, Vincent W V Jaddoe, Marjo-Riitta Järvelin, Nicholas J Timpson, Inga Prokopenko, Rachel M Freathy.
Nat. Genet.
Show Abstract
Hide Abstract
Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits. In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.
Related JoVE Video
A genome-wide association meta-analysis identifies new childhood obesity loci.
Nat. Genet.
Show Abstract
Hide Abstract
Multiple genetic variants have been associated with adult obesity and a few with severe obesity in childhood; however, less progress has been made in establishing genetic influences on common early-onset obesity. We performed a North American, Australian and European collaborative meta-analysis of 14 studies consisting of 5,530 cases (?95th percentile of body mass index (BMI)) and 8,318 controls (<50th percentile of BMI) of European ancestry. Taking forward the eight newly discovered signals yielding association with P < 5 × 10(-6) in nine independent data sets (2,818 cases and 4,083 controls), we observed two loci that yielded genome-wide significant combined P values near OLFM4 at 13q14 (rs9568856; P = 1.82 × 10(-9); odds ratio (OR) = 1.22) and within HOXB5 at 17q21 (rs9299; P = 3.54 × 10(-9); OR = 1.14). Both loci continued to show association when two extreme childhood obesity cohorts were included (2,214 cases and 2,674 controls). These two loci also yielded directionally consistent associations in a previous meta-analysis of adult BMI(1).
Related JoVE Video

What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.