rapid-fractionation-isolation-whole-blood-components-samples-obtained

Rapid Fractionation and Isolation of Whole Blood Components in Samples Obtained from a Community-based Setting

Collection and processing of whole blood samples in a non-clinical setting offers a unique opportunity to evaluate community-dwelling individuals both ...

Wayne State University School of Medicine

Recent work suggests that the 9-repeat (9R) allele located in the 3'UTR VNTR of the SLC6A3 gene increases risk of posttraumatic stress disorder (PTSD). However, no study reporting this association to date has been based on population-based samples. Furthermore, no study of which we are aware has assessed the joint action of genetic and DNA methylation variation at SLC6A3 on risk of PTSD. In this study, we assessed whether molecular variation at SLC6A3 locus influences risk of PTSD. Participants (n = 320; 62 cases/258 controls) were drawn from an urban, community-based sample of predominantly African American Detroit adult residents, and included those who had completed a baseline telephone survey, had provided blood specimens, and had a homozygous genotype for either the 9R or 10R allele or a heterozygous 9R/10R genotype. The influence of DNA methylation variation in the SLC6A3 promoter locus was also assessed in a subset of participants with available methylation data (n = 83; 16 cases/67 controls). In the full analytic sample, 9R allele carriers had almost double the risk of lifetime PTSD compared to 10R/10R genotype carriers (OR = 1.98, 95% CI = 1.02-3.86), controlling for age, sex, race, socioeconomic status, number of traumas, smoking, and lifetime depression. In the subsample of participants with available methylation data, a significant (p = 0.008) interaction was observed whereby 9R allele carriers showed an increased risk of lifetime PTSD only in conjunction with high methylation in the SLC6A3 promoter locus, controlling for the same covariates. Our results confirm previous reports supporting a role for the 9R allele in increasing susceptibility to PTSD. They further extend these findings by providing preliminary evidence that a "double hit" model, including both a putatively reduced-function allele and high methylation in the promoter region, may more accurately capture molecular risk of PTSD at the SLC6A3 locus.

Molecular variation at the SLC6A3 locus predicts lifetime risk of PTSD in the Detroit Neighborhood Health Study.

The role of endoplasmic reticulum (ER) stress response in mental illness is not well understood. Human studies and animal models of depression show elevated brain ER stress response. In addition, some ER stress associated disorders (e.g. cardiovascular disease) show higher rates of depression compared to the general population, raising the possibility that ER stress response contributes to depression risk. It remains unknown, however, if ER stress response is present among individuals suffering from other stress-related mental illness, and whether such a response would be evident in a non-clinical sample. This study tests for systemic changes in ER stress response associated with Major Depressive Disorder (MDD) or post-traumatic stress disorder (PTSD) among community-dwelling individuals.

Elevated systemic expression of ER stress related genes is associated with stress-related mental disorders in the Detroit Neighborhood Health Study.

Prior studies have found that the 5-HTTLPR polymorphism in the promoter region of the serotonin transporter gene (SLC6A4) interacts with stressful life events to increase general risk for PTSD, but this association has not extended to African American samples. Further, little is known about the effects of this interaction on specific PTSD symptom clusters, despite indications that clusters may have different biological substrates. The current study examined the interaction between exposure to childhood emotional abuse and 5-HTTLPR genotype on risk for PTSD symptom severity and severity of specific PTSD symptom clusters in two African American samples.

Associations between the SS variant of 5-HTTLPR and PTSD among adults with histories of childhood emotional abuse: results from two African American independent samples.

Article	Year
Molecular variation at the SLC6A3 locus predicts lifetime risk of PTSD in the Detroit Neighborhood Health Study. PloS one\| PubMed ID: 22745713	2012
Elevated systemic expression of ER stress related genes is associated with stress-related mental disorders in the Detroit Neighborhood Health Study. Psychoneuroendocrinology\| PubMed ID: 24703171	2014
Associations between the SS variant of 5-HTTLPR and PTSD among adults with histories of childhood emotional abuse: results from two African American independent samples. Journal of affective disorders\| PubMed ID: 24751314	2014

Richelo Soliven

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