New susceptibility loci associated with type 2 diabetes. (c2011)

Abstract

Type 2 Diabetes (T2D) is a complex multifactorial disease, characterized by insulin resistance and a progressive pancreatic β cell failure, leading to an increase in fasting plasma glucose level. Up to date and despite the tremendous evolution in genetic research, less than 10% of T2D underlying genetic basis has been identified. Hence the whole picture of T2D inheritance is not completely exposed yet. So far, the mutations recognized, either through the candidate gene approach or recently through the Genome wide association studies, are positioned either in genes regulating the insulin resistance pathway or secretion, or in segments of genes of unknown function. From the most recent mutations identified in 2010, we selected three genes, the Hepatocyte Nuclear factor 1-A (HNF1A) (rs7957197), the High mobility group 2 (HMGA2) (rs1531343) and the Kruppel-like Factors 14 (KLF14) (rs972283) to be the material of our study. Our aim was to identify the polymorphisms related to these genes in the Lebanese diabetic population. 1205 patients were selected (565 diabetic, 640 control subjects) and were genotyped for polymorphisms in HNF1A gene, HMGA2 gene and KLF14 gene. Statistical analysis using chisquare test was utilized to compare the genotype and allele frequencies between the two groups of the study. Our analysis revealed an association between the TT genotype of HNF1Ars7957197 and T2D in the Lebanese diabetic population (P = 0.028) but no significant correlations were detected for KLF14-rs972283 and the HMGA2-rs1531343 (P = 0.27 and 0.58 respectively). Furthermore, when considering the treatment with either insulin or an Oral hypoglycemic agent, significant results were observed in HNF1A-rs7957197, where the risk allele T is more common in patients treated with OHA as compared either to a different type of treatment (P = 0.04) or to treatment with insulin injections (P = 0.03). Similarly, in KLF14-rs972283 polymorphism the genotype GG was found to be correlated with diabetic patients not treated with insulin injections (P = 0.02). In conclusion, the HNF1A-rs7957197 and KLF14-rs972283 mutations could be involved in attenuating the rate of β cell failure. Further studies with a larger Lebanese sample size must be accomplished to confirm our results.