Wang Xue-Bin, Han Ya-di, Cui Ning-Hua, Gao Jia-Jia, Yang Jie, Huang Zhu-Liang, Zhu Qiang, Zheng Fang
Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China.
Department of Clinical Laboratory, Children's Hospital of Zhengzhou, Zhengzhou, 450053, Henan, China.
Lipids Health Dis. 2015 Jul 25;14:80. doi: 10.1186/s12944-015-0079-1.
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.
Six 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.
Among 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.
The 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.
近期全基因组关联研究(GWAS)已鉴定出多个与白种人血脂水平相关的单核苷酸多态性(SNP)。本研究调查这些基因座是否影响中国人群的血脂水平,以及它们是否与冠状动脉疾病(CAD)风险及其血管造影严重程度相关。
采用高分辨率熔解(HRM)法对1100例CAD患者和1069例对照进行6个SNP的基因分型。通过血管评分和Gensini评分系统评估冠状动脉粥样硬化严重程度。
在6个SNP和遗传风险评分(GRS)中,HNF1A rs1169288的次要等位基因(比值比(OR)=1.18,95%置信区间(CI)1.05 - 1.33,P = 0.006)、MADD - FOLH1 rs7395662的次要等位基因(OR = 1.20,95% CI 1.07 - 1.36,P = 0.002)以及GRS(P = 1.06×10⁻⁵)在错误发现率(FDR)校正后与CAD风险增加显著相关。不同SNP rs1169288 C>T基因型的CAD患者血管评分(P = 0.013)和Gensini评分(β = 0.113,P = 0.002)存在差异。采用加性模型的多元线性回归分析显示,SNP rs1169288的次要等位基因C(β = 0.060,P = 0.001)和GRS(β = 0.033,P = 3.59×10⁻⁴)与总胆固醇(TC)水平升高显著相关,SNP rs7395662的次要等位基因A(β = -0.024,P = 0.007)和GRS(β = -0.013,P = 0.004)与高密度脂蛋白胆固醇(HDL - c)水平降低显著相关。
本研究表明,SNP rs1169288、rs7395662和GRS与中国人群的血脂水平及CAD风险显著相关。此外,SNP rs1169288的等位基因C增加了冠状动脉粥样硬化严重程度的几率。