载脂蛋白C3基因rs2854116、rs2854117、rs5128位点单核苷酸多态性与代谢综合征相关性研究

Associations of the apolipoprotein C3 rs2854116,rs2854117 and rs5128 single nucleotide polymorphisms with metabolic syndrome

目的探讨中国汉族人群中载脂蛋白C3(apolipoprotein C3,APOC3)基因rs2854116、rs2854117、rs5128位点单核苷酸多态性(single nucleotide polymorphisms,SNPs)与代谢综合征(metabolic syndrome,MS)的相关性。方法在具有代表性的南京市城乡居民营养与健康状况调查人群基础上,通过性别、年龄匹配的病例对照设计,利用外周血白细胞DNA测定各位点SNPs,调整人口学特征和生活方式因素基础上,采用多因素非条件logistic回归分析APOC3基因rs2854116、rs2854117、rs5128位点SNPs和MS的关系。结果纳入MS组和对照组各253例,两组间除文化程度和高血压家族史构成外,其他人口学特征构成差异无统计学意义(P>0.05)。rs2854116、rs2854117和rs5128位点SNPs在共显性(OR=2.219,95%CI:1.163~4.234;OR=2.619,95%CI:1.336~5.136;OR=4.152,95%CI:1.651~10.442)和显性(OR=1.782,95%CI:1.083~2.934;OR=1.721,95%CI:1.064~2.783;OR=1.702,95%CI:1.048~2.763)遗传模型下与MS存在相关性,rs2854117、rs5128位点SNPs在隐性遗传模型下与MS存在相关性(OR=2.054,95%CI:1.131~3.731;OR=4.925,95%CI:1.860~13.043)。各位点间存在连锁不平衡,rs2854117-rs2854116位点C-T(χ^(2)=7.061,P=0.008)、T-C(χ^(2)=17.365,P<0.001)、T-T(χ^(2)=4.208,P=0.040)单倍型频率,rs2854116-rs5128位点C-G(χ^(2)=10.720,P=0.001)、T-C(χ^(2)=14.911,P<0.001)单倍型频率,rs2854117-rs2854116-rs5128位点C-T-C(χ^(2)=13.271,P<0.001)、T-C-G(χ^(2)=14.896,P<0.001)单倍型频率在MS组和对照组间差异均有统计学意义。rs2854116、rs2854117、rs5128三个位点间交互作用三阶模型最佳,交叉验证一致性10/10,差异有统计学意义(P=0.011)。结论APOC3基因rs2854116、rs2854117、rs5128位点SNPs在中国汉族人群中与MS患病有关联,且各位点间可能存在交互作用。

Objective To explore the relationships of single nucleotide polymorphisms(SNPs)at rs2854116,rs2854117 and rs5128 loci of the apolipoprotein C3(APOC3)gene with metabolic syndrome(MS)in Chinese Han population.Methods Based on a representative survey on the status of nutrition and health among urban and rural residents in Nanjing City,a case-control study matched by gender and age was conducted.Peripheral blood leukocyte DNA was extracted to determine SNPs at each locus.After adjusting the demographic characteristics and lifestyle factors,multivariate unconditional logistic regression was used to analyze the relationships of SNPs at rs2854116,rs2854117 and rs5128 loci of the APOC3 gene with MS.Results The cases enrolled were divided into the MS group and the control group(each n=253).No statistically significant differences were found in the composition of demographic characteristics between the two groups(P>0.05)except for education level and family history of hypertension.The SNPs at rs2854116,rs2854117 and rs5128 loci were correlated with MS in both codominant(OR=2.219,95%CI:1.163-4.234;OR=2.619,95%CI:1.336-5.136;OR=4.152,95%CI:1.651-10.442)and dominant models(OR=1.782,95%CI:1.083-2.934;OR=1.721,95%CI:1.064-2.783;OR=1.702,95%CI:1.048-2.763).The SNPs at rs2854117 and rs5128 loci were correlated with MS in recessive model(OR=2.054,95%CI:1.131-3.731;OR=4.925,95%CI:1.860-13.043).There was a linkage imbalance among the loci.The frequencies of C-T(χ^(2)=7.061,P=0.008),T-C(χ^(2)=17.365,P<0.001)and T-T(χ^(2)=4.208,P=0.040)haplotypes at rs2854117-rs2854116,C-G(χ^(2)=10.720,P=0.001),T-C(χ^(2)=14.911,P<0.001)haplotypes at rs2854116-rs5128,and C-T-C(χ^(2)=13.271,P<0.001)and T-C-G(χ^(2)=14.896,P<0.001)haplotypes at rs2854117-rs2854116-rs5128 showed statistically significant differences between the MS group and the control group.The three-order interaction model of rs2854116,rs2854117 and rs5128 was the best,and the cross-validation agreement was 10/10,with statistically significant differences(P=0.011).Conclusion The SNPs at rs2854116,rs2854117 and rs5128 loci of the APOC3 gene are associated with MS incidence in Chinese Han population,and there may be interaction among these loci.