Polymorphism of Diabetes Mellitus in Iran (A review)

Background and Objective Diabetes Mellitus(DM) is a common metabolic disorder presenting increased amounts of serum glucose and will cover 5.4% of population by year 2025and in 2012 ,4.8million people died owing to diabetes. In addition, 75% of diabetic patients will be inhabited in developing countries. Similarly, in Iran diabetes is a major health problem. Genetic variation can impact on efficacy and risk of adverse events to commonly used oral agents in diabetes. Pharmacogenetics is the study of genetic polymorphisms affecting responses to drug therapy.Search MethodInitial searching was conducted using related keywords such as ‘’Diabetes’’ ,‘’pharmacogenetics of type 2 diabetes (T2D)’’ and ‘’ Diabetes mellitus’’ and ‘’polymorphism’’ in databases including Pub med and Google scholar. Papers conducted in Iran and published between 2010 and 2016 were collected and reviewed. Findings The common rs7903146 (C.T) polymorphism of the TCF7L2 gene has recently been associated with type 2 diabetes (T2D).In that study, the frequency of the homozygous (T/T) variant of rs7903146(C.T) was high in the Fars ethnicity, but low in the Lure, similar to that of ethnic Turk and Kurd. The rs7903146 polymorphism was found with a frequency of 0.37 in the Iranian population, which is higher than the Asian Indians,25 Mexicans,12 Italians,34 Polish. Insulin secretion pathway starts with potassium channels in pancreatic beta cells. KCNJ11 gene encodes ATP-sensitive potassium channel subunits. That study suggests that KCNJ11 (E23K) gene polymorphism is associated with T2DM. Moreover, Several single nucleotide polymorphisms (SNPs) of ABCC8 gene and their interaction are involved in pathogenicity of DM. Additionally, The possession of both MTHFR 677T and 1298C alleles increase the risk of microalbuminuria to 4.3-fold (p = 0.007) in T2DM patients. The presence of either MTHFR 677T, 1298C allele is sufficient to increase the risk of macroalbuminuria in T2DM patients. There have been inconsistent reports about SNPs of the adiponectin gene and risk of type 2 diabetes (T2DM) as well. Several single nucleotide polymorphisms (SNPs) of ABCC8 gene and their interaction are involved in pathogenicity of DM.ConclusionIn conclusion, this review demonstrates the presence of the rs7903146, KCNJ11, MTHFR, adiponectin, and ABCC8 polymorphism in the Iranian population, suggesting susceptibility to T2D and adverse or poor drug responses, which may lead to increase in mortality risk.

Keywords:

pharmacogenetics of type 2 diabetes (T2D) , Diabetes mellitus , polymorphism