Disease risk and preventive medical evaluation of gene polymorphism in relation to hyperlipidemia and diabetes mellutus

高脂血症、糖尿病相关基因多态性的疾病风险及预防医学评价

• 批准号: 17590509
• 负责人: SUWAZONO Yasushi
• 金额: $ 2.3万
• 依托单位: Chiba University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590509/
• 关键词: Genetic polymorphism; Hyperlipidemia; Diabetes mellitus

We examined the relationship between the A1330V and Q89R variants in the low-density lipoprotein receptor-related protein 5 (LRP5) gene, and the risk of hypercholesterolemia in a prospective study in Japanese workers. This study included observations over a 5-year period from 1997 to 2002 on 956 males and 662 females who were not hypercholesterolemic on entry. Hypercholesterolemia was defined as a serum total cholesterol level ≧240 mg/dL. Pooled logistic regression analyses were performed using either of the gene variants with age, body mass index, smoking, alcohol consumption and habitual exercise as the covariates. The risk of the development of hypercholesterolemia was 1.49 times higher in males with the AV genotype of LRP5/A1330V than in males with the AA genotype (95% confidence interval : 1.04-2.12) after adjustment for the effects of other potential covariates. Furthermore, the C1429T of G-protein beta 3 subunit variant was an independent significant risk factors for hypercholesterolemia as well. Therefore, pooled logistic regression analyses were performed again to examine the association between the combination of polymorphisms and hypercholesterolemia using age, body mass index, smoking, alcohol consumption and habitual exercise as covariates that had potential to affect cholesterol levels. The odd ratios in males and females with GNB3/1429TT and LRP5/1330VV or AV genotypes were 4.17 compared to males with the 1429CT or TT and 1330AA genotypes and 3.53 compared to females with the 1429CC, CT or TT and 1330AA genotypes. This study indicates that the combination of GNB3/C1429T and LRP5/A1330V is a very useful marker for predicting the development of hypercholesterolemia in the general Japanese population.

我们检查了在日本工人的一项前瞻性研究中，我们研究了低密度脂蛋白受体相关蛋白5（LRP5）基因的A1330V和Q89R变体之间的关系，以及高胆固醇血症的风险。这项研究包括从1997年到2002年的5年期间对956名男性和662名女性的观察，这些男性在进入时并非高胆固醇。高胆固醇血症定义为血清总胆固醇水平≧240mg/dL。汇总的逻辑回归分析是使用年龄，体重指数，吸烟，饮酒和习惯性运动的任何基因变体进行的，作为协变量。在调整其他潜在协变量的影响后，患有LRP5/A1330V的AV基因型的高胆固醇血症的风险比具有AA基因型（95％置信区间：1.04-2.12）的男性高1.49倍。此外，G蛋白β3亚基变体的C1429T也是高胆固醇血症的独立重要危险因素。因此，再次进行了汇总的逻辑回归分析，以检查多态性和高胆固醇血症的结合使用年龄，体重指数，吸烟，酒精消耗和习惯运动，因为有可能影响胆固醇水平的协变量。与具有1429CT或TT和1330AA基因型的男性相比，与1429CT或1330AA基因型的男性相比，男性和女性的奇数比为4.17，与1429cc，1429cc，CT OR TT或TT和1330AA基因组相比，与1429CT或1330AA基因型和3.53相比，GNB3/1429TT和LRP5/1330VV或AV基因型的奇数比为4.17。这项研究表明，GNB3/C1429T和LRP5/A1330V的组合是预测日本普通人群中高胆固醇血症的发展非常有用的标记。