A new susceptibility locus for myocardial infarction, hypertension, type 2 diabetes mellitus, and dyslipidemia on chromosome 12q24

Abstract

We examined the role of hepatic nuclear factor-1 alpha (HNF1a) gene polymorphism on coronary artery disease (CAD) traits in 4631 Saudi angiographed individuals (2419 CAD versus 2212 controls) using TaqMan assay on ABI Prism 7900HT sequence detection system. Following adjustment for confounders, the rs2259820-CC (1.19 (1.01-1.42); P = 0.041), rs2464196-TT (1.19 (1.00-1.40); P = 0.045), and rs2259816-T (1.13 (1.01-1.26); P = 0.031) were associated with MI. The rs2259820-T (1.14 (1.03-1.26); P = 0.011) and rs2464196-C (1.12 (1.02-1.24); P = 0.024) were associated with type 2 diabetes mellitus (T2DM), while the rs2393791-T (1.14 (1.01-1.28); P = 0.032), rs7310409-G (1.16 (1.03-1.30); P = 0.013), and rs2464196-AG+GG (1.25 (1.05-1.49); P = 0.012) were implicated in hypertension. Hypertriglyceridemia was linked to the rs2393791-T (1.14 (1.02-1.27); P = 0.018), rs7310409-G (1.12 (1.01-1.25); P = 0.031), rs1169310-G (1.15 (1.04-1.28); P = 0.010), and rs1169313-CT+TT (1.24 (1.06-1.45); P = 0.008) and high low density lipoprotein-cholesterol levels were associated with rs2259820-T (1.23 (1.07-1.41); P = 0.004), rs2464196-T (1.22 (1.06-1.39); P = 0.004), and rs2259816-T (1.18 (1.02-1.36); P = 0.023). A 7-mer haplotype CATATAC (χ 2 = 7.50; P = 0.0062), constructed from the studied SNPs, was associated with MI, and CATATA implicated in T2DM (χ 2 = 3.94; P = 0.047). Hypertriglyceridemia was linked to TGCGGG (χ 2 = 4.26; P = 0.039), and obesity to ACGGGT (χ 2 = 5.04; P = 0.025). Our results suggest that the HNF1a is a common susceptibility gene for MI, T2DM, hypertension, and dyslipidemia. © 2014 Salma M. Wakil et al.