Abstract
BackgroundRecent genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) that were associated with blood lipid levels in Caucasians. This study investigated whether these loci influenced lipid levels and whether they were associated with the risk of coronary artery disease (CAD) and its angiographic severity in Chinese population.MethodsSix SNPs were genotyped in 1100 CAD cases and 1069 controls using the high-resolution melting (HRM) method. Coronary atherosclerosis severity was assessed by the vessel scores and the Gensini scoring system.ResultsAmong the 6 SNPs and the genetic risks scores (GRS), the minor alleles of HNF1A rs1169288 (odd ratio (OR) = 1.18, 95 % confidence interval (CI) 1.05–1.33, P = 0.006) and MADD-FOLH1 rs7395662 (OR = 1.20, 95 % CI 1.07–1.36, P = 0.002) as well as the GRS (P = 1.06 × 10-5) were significantly associated with increased risk of CAD after false discovery rate (FDR) correction. The vessel (P = 0.013) and Gensini scores (β = 0.113, P = 0.002) differed among CAD patients with different SNP rs1169288 C > T genotypes. The multiple linear regression analyses using an additive model revealed that the minor allele C of SNP rs1169288 (β = 0.060, P = 0.001) and the GRS (β = 0.033, P = 3.59 × 10-4) were significantly associated with increased total cholesterol (TC) levels, the minor allele A of SNP rs7395662 (β = -0.024, P = 0.007) and the GRS (β = -0.013, P = 0.004) were significantly associated with decreased high-density lipoprotein cholesterol (HDL-c) levels.ConclusionsThe present study demonstrated that SNPs rs1169288, rs7395662 and the GRS were significantly associated with lipid levels and the risk of CAD in Chinese population. Furthermore, the allele C of SNP rs1169288 increased the odds of coronary atherosclerosis severity.Electronic supplementary materialThe online version of this article (doi:10.1186/s12944-015-0079-1) contains supplementary material, which is available to authorized users.
Highlights
Recent genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) that were associated with blood lipid levels in Caucasians
Blood pressure (BP), plasma concentrations of glucose, total cholesterol (TC), TG, C-reactive protein (CRP) levels, body mass index (BMI) and the prevalence of overweight and obesity were significantly higher, while high-density lipoprotein cholesterol (HDL-c) levels were significantly lower in the case group than those of the control group
Under an additive model adjusted for age, sex, alcohol intake, smoking and weight status, the minor allele C of HNF1A rs1169288 was significantly associated with increased TC levels (β = 0.060, SE = 0.018, P = 0.001) and
Summary
Recent genome-wide association studies (GWAS) have identified several single nucleotide polymorphisms (SNPs) that were associated with blood lipid levels in Caucasians. This study investigated whether these loci influenced lipid levels and whether they were associated with the risk of coronary artery disease (CAD) and its angiographic severity in Chinese population. SNP rs9411489, which is located 4.3 kb downstream of the ABO blood group (ABO) gene, was found to be associated with lipid levels in a GWAS of Europeans [10]. A large-scale association analysis in individuals of European descent identified the following three variants associated with lipid levels and CAD risk: SNPs rs1169288, rs1495741 and rs10128711, which located in or near the hepatocyte nuclear factor 1-α (HNF1A) gene, N-acetyltransferase 2 (NAT2) gene and SPT2, Suppressor of Ty, domain containing 1 (SPTY2D1) gene, respectively [11]
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