Major depression (MD) has a complex multifactorial etiology with genetic and environmental factors contributing to the disorder. As with all antidepressant treatments, there is variability in drug response due to heredity, generally focusing on genetic polymorphism of the drug-metabolizing transporter genes. The serotonin transporter (5-HTT) gene is a particularly important candidate for genetic involvement in MD disorders owing to its key role in the regulation of serotonergic transmission and is therefore considered to be an interesting candidate in the mechanism of antidepressant drugs. In this study, we have focused on the associations between genetic polymorphisms in two regions of the 5-HTT gene (5-HTTLPR and VNTR) related to sertraline responses. Our sample consisted of 64 unrelated Turkish subjects who strictly met DSM-IV and CGI scores. There was no significant difference between the frequency of the SS, LS, LL, 9/10, 10/10, 9/12, 10/12, and 12/12 genotypes and responses to sertraline. However, the number of patients can be increased and different drugs can be studied in order to find a specific pharmacogenetic relation.
26 March 2014 in American Journal of Medical Genetics Part A
Aim. The present study was designed to examine the relationship between Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-γ gene (PPAR-γ) and clinical and hormonal characteristics in women with polycystic ovary syndrome (PCOS). Materials and methods. One hundred patients with PCOS and 100 healthy subjects were included in the study. Serum levels of sex steroids were measured. Insulin resistance was evaluated by homeostasis model assessment (HOMA). The responses of glucose and insulin to an oral glucose tolerance test were analyzed by calculating the respective area under the curve (AUC) by the trapezoidal method. We used the restriction fragment length polymorphism technique and polymerase chain reaction to examine Pro12Ala polymorphism in exon 2 of PPAR-γ. Results. Pro12Ala polymorphism of PPAR-γ was significantly elevated in control subjects (22%) compared with PCOS subjects (15%). All of the Pro12Ala polymorphisms of PPAR-γ were heterozygous. When PCOS subjects with the Pro allele and the Ala allele of PPAR-γ were compared, the latter had lower free testosterone, androstenedione, dehydroepiandrosterone sulfate, insulin and C-peptide levels, as well as lower luteinizing hormone/follicle-stimulating hormone ratio, HOMA insulin resistance index, AUCinsulin, Ferriman–Gallwey score, acne, body mass index and waist-to-hip ratio. Conclusion. We suggest that Pro12Ala polymorphism of the PPAR-γ gene may be a modifier of insulin resistance in women with PCOS.