Institute of Occupational Medicine and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Huazhong University of Science and Technology, Wuhan, Hubei, China.
PLoS One. 2011;6(11):e27481. doi: 10.1371/journal.pone.0027481. Epub 2011 Nov 14.
Recent genome-wide association studies (GWAS) have mapped several novel loci influencing blood lipid levels in Caucasians. We sought to explore whether the genetic variants at newly identified lipid-associated loci were associated with CHD susceptibility in a Chinese Han population.
METHODOLOGY/PRINCIPAL FINDINGS: We conducted a two-stage case-control study in a Chinese Han population. The first-stage, consisting of 1,376 CHD cases and 1,376 sex and age- frequency matched controls, examined 5 novel lipid-associated single-nucleotide polymorphisms (SNPs) identified from GWAS among Caucasians in relation to CHD risk in Chinese. We then validated significant SNPs in the second-stage, consisting of 1,269 cases and 2,745 controls. We also tested associations between SNPs within the five novel loci and blood lipid levels in 4,121 controls. We identified two novel SNPs (rs599839 in CELSR2-PSRC1-SORT1 and rs16996148 in NCAN-CILP2) that were significantly associated with reduced CHD risk in Chinese (odds ratios (95% confidence intervals) in the dominant model 0.76 (0.61-0.90; P = 0.001), 0.67 (0.57-0.77; P = 3.4×10(-8)), respectively). Multiple linear regression analyses using dominant model showed that rs599839 was significantly associated with decreased LDL levels (P = 0.022) and rs16996148 was significantly associated with increased LDL and HDL levels (P = 2.9×10(-4) and 0.001, respectively).
CONCLUSIONS/SIGNIFICANCE: We identified two novel SNPs (rs599839 and rs16996148) at newly identified lipid-associated loci that were significantly associated with CHD susceptibility in a Chinese Han population.
最近的全基因组关联研究（GWAS）已经确定了一些影响白种人血脂水平的新基因座。我们试图探索在汉族人群中，新鉴定的脂质相关基因座的遗传变异是否与冠心病易感性有关。
方法/主要发现：我们在中国汉族人群中进行了两阶段病例对照研究。第一阶段包括 1376 例冠心病病例和 1376 例性别和年龄频数匹配的对照，研究了在白种人中通过 GWAS 鉴定的 5 个新的脂质相关单核苷酸多态性（SNP）与中国汉族人冠心病风险的关系。然后，我们在第二阶段对 1269 例病例和 2745 例对照中显著的 SNP 进行了验证。我们还在 4121 例对照中检测了这 5 个新基因座内的 SNP 与血脂水平之间的关系。我们发现了两个新的 SNP（CELSR2-PSRC1-SORT1 中的 rs599839 和 NCAN-CILP2 中的 rs16996148）与中国人冠心病风险降低显著相关（在显性模型中，优势比（95%置信区间）分别为 0.76（0.61-0.90；P=0.001）和 0.67（0.57-0.77；P=3.4×10(-8)））。采用显性模型的多元线性回归分析显示，rs599839 与 LDL 水平降低显著相关（P=0.022），rs16996148 与 LDL 和 HDL 水平升高显著相关（P=2.9×10(-4)和 0.001）。
结论/意义：我们在新鉴定的脂质相关基因座中发现了两个与汉族人群冠心病易感性显著相关的新 SNP（rs599839 和 rs16996148）。
