Evaluation of the HNF1a gene as a risk factor for metabolic syndrome in the Saudi population

Abstract

The hepatic nuclear factor 1 alpha (HNF1a) is found predominantly in the liver and pancreatic islet cells where it regulates tissue specific expression of several genes involved in metabolic syndrome pathways. While the HNF1a has been associated with type 2 diabetes mellitus and elevated susceptibility to coronary artery disease, its role in the onset and development of the latter is yet to be clearly explained. We selected 7 familial SNPs to evaluate the role of the HNF1a gene in metabolic risk factors, such as type 2 diabetes mellitus (T2DM), hypertension, obesity and dyslipidaemia. The rs2259820 T [1.10(1.01–1.20); p=0.024] and its dominant mode of inheritance rs2259820 (CT+TT) [1.18(1.03–1.35); p=0.020] conferred risk for T2DM (2550 cases vs 2081 controls). The rs1169310 G [1.10(1.00–1.22); p=0.045] and rs1169313 T [1.11(11.01–1.22); p=0.038] conferred risk for hypertriglyceridaemia (hTG; 1160 vs 3156). On the other hand, rs2464196 T [0.92(0.84–1.00); p=0.039], and rs2464196 TT [0.86(0.75–0.99); p=0.030] were protective against acquiring the disease. Furthermore, the rs7310409 (AG+GG) (p=0.023) and rs2393791 (CT+TT) (p=0.041) were protective against acquiring hypercholesterolaemia, and rs1169310 G (p=0.045) against hTG. Our data suggests that NHF1a is a risk factor for metabolic syndrome.