Yamada Y, Ichihara S, Kato K, Yoshida T, Yokoi K, Matsuo H, Watanabe S, Metoki N, Yoshida H, Satoh K, Aoyagi Y, Yasunaga A, Park H, Tanaka M, Lee W, Nozawa Y
Department of Human Functional Genomics, Life Science Research Center, Mie University, 1577 Kurima-machiya, Tsu, Mie 514-8507, Japan.
J Med Genet. 2008 Jan;45(1):22-8. doi: 10.1136/jmg.2007.052415. Epub 2007 Aug 31.
The aetiology of metabolic syndrome is complex, being determined by the interplay of both genetic and environmental factors. The aim of this study was to identify genetic polymorphisms that confer susceptibility to metabolic syndrome, to allow prediction of genetic risk for this condition.
The study population comprised 2417 unrelated Japanese subjects (1522 with metabolic syndrome and 895 controls). The genotypes for 44 polymorphisms of 31 candidate genes related to lipid metabolism were determined using a combination of PCR and sequence-specific oligonucleotide probes with suspension array technology.
The chi(2) test and subsequent multivariate logistic regression analysis with adjustment for age, sex and smoking status found that the-3A-->G and 553G-->T (Gly185Cys) polymorphisms of APOA5, the 2052T-->C (Val653Val) and 1866C-->T (Asn591Asn) polymorphisms of LDLR, the 13989A-->G (Ile118Val) polymorphism of CYP3A4 and the 1014T-->A polymorphism of C1QTNF5 were significantly (false discovery rate <0.05) associated with the prevalence of metabolic syndrome, with the variant alleles of APOA5 and C1QTNF5 representing risk factors for and those of LDLR and CYP3A4 being protective against this condition. Serum levels of triglycerides and high-density lipoprotein (HDL) cholesterol differed significantly (p<0.05) among APOA5 genotypes; the serum level of HDL cholesterol differed among LDLR genotypes; and the fasting plasma glucose level and body mass index differed between CYP3A4 and C1QTNF5 genotypes, respectively.
APOA5, LDLR, CYP3A4 and C1QTNF5 are susceptibility loci for metabolic syndrome in Japanese people. Genotypes for these polymorphisms may prove informative for prediction of genetic risk for metabolic syndrome.
代谢综合征的病因复杂，由遗传和环境因素的相互作用决定。本研究的目的是确定赋予代谢综合征易感性的基因多态性，以便预测这种疾病的遗传风险。
研究人群包括2417名无亲缘关系的日本受试者（1522名患有代谢综合征，895名作为对照）。使用聚合酶链反应（PCR）和序列特异性寡核苷酸探针结合悬浮阵列技术，确定了31个与脂质代谢相关的候选基因的44个多态性的基因型。
卡方检验以及随后对年龄、性别和吸烟状况进行调整的多因素逻辑回归分析发现，载脂蛋白A5（APOA5）的-3A→G和553G→T（Gly185Cys）多态性、低密度脂蛋白受体（LDLR）的2052T→C（Val653Val）和1866C→T（Asn591Asn）多态性、细胞色素P450 3A4（CYP3A4）的13989A→G（Ile118Val）多态性以及C1q肿瘤坏死因子5（C1QTNF5）的1014T→A多态性与代谢综合征的患病率显著相关（错误发现率<0.05），APOA5和C1QTNF5的变异等位基因代表代谢综合征的危险因素，而LDLR和CYP3A4的变异等位基因对这种疾病具有保护作用。不同APOA5基因型之间的甘油三酯和高密度脂蛋白（HDL）胆固醇血清水平存在显著差异（p<0.05）；不同LDLR基因型之间的HDL胆固醇血清水平存在差异；CYP3A4和C1QTNF5基因型之间的空腹血糖水平和体重指数分别存在差异。
APOA5、LDLR、CYP3A4和C1QTNF5是日本人代谢综合征的易感基因座。这些多态性的基因型可能对预测代谢综合征的遗传风险具有参考价值。
