Association of the HNF1A polymorphisms and serum lipid traits, the risk of coronary artery disease and ischemic stroke.

BACKGROUND: Hepatocyte nuclear factor-1α gene (HNF1A) single nucleotide polymorphisms (SNPs) have been associated with serum lipid traits in several previous genome-wide association studies. However, little is known about such associations in the Chinese populations. The present study aimed to determine the association of the HNF1A rs1169288, rs2259820, rs2464196 and rs2650000 SNPs and serum lipid traits, the risk of coronary artery disease (CAD) and ischemic stroke (IS).

METHODS: The genotypes of the four SNPs in 562 CAD and 521 IS patients, as well as 594 healthy controls, were detected using the Snapshot technology.

RESULTS: The genotype and allele distribution of the four SNPs was not different between controls and CAD or IS patients (p > 0.05 for all). rs1169288, rs2259820 and rs2464196 SNPs were significantly associated with serum lipid levels in both controls and CAD patients (p < 0.004-0.009). rs2259820 and rs2464196 SNPs were significantly associated with a lower risk of CAD [odds ratio (OR) = 0.64, 95% confidence interval (CI) = 0.44-0.91, p = 0.015 and OR =0.62, 95% CI = 0.43-0.89, p = 0.010, respectively]. Significant linkage disequilibrium was noted among the four SNPs (r2  > 0.5, D' > 0.8). The haplotype of rs1169288A-rs2259820C-rs2464196G-rs2650000A was associated with an increased risk of CAD (OR =1.95, 95% CI: 1.13-3.37, p = 0.015). Interactions of SNP-SNP (rs1169288-rs2464196-rs2650000) and haplotype-environment on the risk of CAD (A-C-G-A-smoking) or IS (A-C-G-A-sex and A-T-A-C-alcohol consumption) were also observed among these SNPs.

CONCLUSIONS: These findings suggest that the HNF1A polymorphisms may be the genetic risk factors for CAD and IS.