Genetic Risk Analysis of Gestational Diabetes Mellitus in a Turkish Population

Background: Gestational diabetes mellitus (GDM) is a type of clinical diabetes characterized by insulin resistance and impaired insulin secretion because of environmental and genetic factors. The high risk of developing type ۲ diabetes (T۲D) in women with GDM and the high risk of developing GDM in women with a family history of T۲D suggests that both diseases may have the same genetic basis. Therefore, genes and risk variants associated with the genetic architecture of T۲D are being investigated for their effects on the development of GDM. In this study, we aim to investigate ABCC۸, TCF۷L۲, Adiponectin, IRS۱, and PPARG genes, which are known as T۲D risk genes, to understand the genetic basis of GDM in a Turkish population. Materials and Methods: In our study, ۷۴ pregnant women diagnosed with GDM according to the American Diabetes Association criteria and ۴۹ healthy pregnant women were included. DNA isolations were made from peripheral blood cells collected from pregnant women and regions of targeted genes were scanned by the Polimerase Chain Reaction-Restriction fragment length polymorphism (PCR-RFLP) technique. The homeostatic model assessment for insulin resistance (HOMA-IR), which is an indicator of insulin resistance, was calculated for each individual in the biochemical examinations. The associations of genotypes detected in the target gene regions with the disease and their effects on the biochemical phenotypes were analyzed by establishing the dominant, recessive, and additive models along with calculating odd ratios. The P<۰.۰۵ was considered statistically significant in all analyses. Results: A statistically significant association was found between R۱۲۷۳R substitution in the ABCC۸ gene and GDM under dominant and additive models. No statistically significant correlation was found between the A۱۳۶۹S and e۱۶/-۳t→c variants in the ABCC۸ gene and the screened variants in other genes and GDM. When the genotype-phenotype association data was evaluated, no association was detected between all the scanned variants and fasting blood sugar while a weak correlation was found between e۱۶/-۳t→c in the ABCC۸ gene and fasting insulin (P=۰.۰۷۵) and HOMA-IR (P=۰.۰۶۷). Conclusion: ABCC۸ (R۱۲۷۳R and e۱۶/-۳t→c) gene variants may be a risk factor for the development of GDM in the Turkish population.

Keywords:

Gestational diabetes , ABCC۸ gene , TCF۷L۲ gene , Adiponectin gene , PPARG gene , IRS۱ gene