In those with the methylenetetrahydrofolate reductase (MTHFR) 677TT genotype, enzyme activity is lowered. Therefore, these individuals might require an increased intake of folate to maintain or control blood levels of plasma folate or total homocysteine (tHcy). We examined associations of dietary folate intake with fasting plasma folate and total homocysteine (tHcy) according to genotype among 554 Japanese (207 men and 347 women aged 39-89 y) recruited in 2009. Intake of folate was estimated with a food frequency questionnaire. The MTHFR polymorphism was genotyped by a polymerase chain reaction with confronting two-pair primers. The log-transformed concentration of folate or tHcy was regressed on energy-adjusted folate intake in a linear regression analysis. Higher folate intake was associated with higher plasma folate among those with the CC (?=0.165, p=0.066) or CT (?=0.248, p<0.001) genotypes, and with lower tHcy levels only among those with the CC (?=-0.141, p=0.013) genotype. Plasma folate was significantly and inversely associated with tHcy, irrespective of MTHFR genotype. When the analysis was restricted to those with tHcy levels higher than the reference range (?13.5 nmol/mL, n=20), these significant associations were not found. The interaction between folate intake or plasma folate and genotype was not significant in any analysis. In conclusion, dietary folate intake was positively associated with plasma folate among those with the CC or CT genotypes and inversely associated with tHcy among those with the CC genotype, but the associations were not clear among those with higher levels of tHcy.
Recently, genetic analyses indicated the association between gout and cGMP-dependent protein kinase 2 (cGKII/PRKG2) gene in a Fukien-Taiwanese heritage population. However, no replication study has been reported in other ancestries. Therefore, we investigated this association in a Japanese population.
Sex chromosome dosage compensation (DC) is widely accepted in various organisms. This concept is mostly supported by comparisons of gene expression between chromosomes and between sexes. However, genes on the X chromosome and autosomes are mostly not homologous, and the average gene expression level on these chromosomes may not be the same even under DC, which complicates comparisons between chromosomes. Many genes with sex-biased expression also make comparisons between sexes difficult. To overcome these issues, we investigated DC by comparing the expression of neo-X-linked genes in Drosophila pseudoobscura with those of their autosomal orthologs in other Drosophila species. The ratio of the former to the latter in males would be 1 under DC, whereas it becomes 0.5 without DC. We found that the ratio was ?0.85 for adult whole bodies, indicating that the DC is incomplete on the neo-X chromosome in adults as a whole. The ratio (?0.90) was also significantly less than 1 for adult bodies without gonads, whereas it was ?1.0 for adult heads. These results indicate that DC varies among tissues. Our sliding-window analysis of the ratio also revealed that the upregulation of neo-X-linked genes in males occurred chromosome wide in all tissues analyzed, indicating global upregulation mechanisms. However, we found that gene functions also affected the levels of DC. Furthermore, most of the genes recently moved to the X were already under DC at the larval stage but not at the adult stage. These results suggest that DC in Drosophila species operates in a tissue/stage-dependent manner.
Semaphorin-4D (Sema4D), a member of class 4 membrane-bound Semaphorins, acts as a chemorepellant to the axons of retinal ganglion cells and hippocampal neurons. Plexin-B1, a neuronal Sema4D receptor, associates with either one of receptor tyrosine kinases, c-Met or ErbB2, to mediate Sema4D-signaling. In contrast to this significance, the involvement of protein tyrosine phosphatases in Semaphorin-signaling remains unknown. We here show that Src homology 2-containing protein-tyrosine phosphatase 2 (SHP2) participates in Sema4D-signaling. SHP2 was localized in the growth cones of chick embryonic retinal ganglion neurons. Phenylarsine oxide, a protein tyrosine phosphatase inhibitor, suppressed Sema4D-induced contractile response in COS-7 cells expressing Plexin-B1. Ectopic expression of a phosphatase-inactive mutant of SHP2 in the retinal ganglion cells attenuated Sema4D-induced growth cone collapse response. A SHP1/2 specific inhibitor, 8-hydroxy-7-(6-sulfonaphthalen-2-yl)diazenyl-quinoline-5-sulfonic acid (NSC-87877), also suppressed this collapse response. These results suggest that SHP2-mediated tyrosine dephosphorylation is an important step in Sema4D-induced axon repulsion.
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