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.

我们在日本工人中进行的一项前瞻性研究中检查了低密度脂蛋白受体相关蛋白5（LRP 5）基因中A1330 V和Q89 R变体与高胆固醇血症风险之间的关系。这项研究包括从1997年至2002年5年期间对956名男性和662名女性的观察，这些人在入组时没有高胆固醇血症。高胆固醇血症定义为血清总胆固醇水平<240 mg/dL。采用两种基因变体中的任一种，以年龄、体重指数、吸烟、饮酒和习惯性运动作为协变量，进行了汇总logistic回归分析。在调整其他潜在协变量的影响后，LRP 5/A1330 V的AV基因型男性患高胆固醇血症的风险是AA基因型男性的1.49倍（95%置信区间：1.04-2.12）。G蛋白β 3亚基C1429 T变异也是高胆固醇血症的独立危险因素。因此，再次进行了汇总logistic回归分析，以检查多态性组合与高胆固醇血症之间的关联，使用年龄，体重指数，吸烟，饮酒和习惯性运动作为可能影响胆固醇水平的协变量。GNB 3/1429 TT和LRP 5/1330 VV或AV基因型的男性和女性与1429 CT或TT和1330 AA基因型的男性相比的比值比为4.17，与1429 CC、CT或TT和1330 AA基因型的女性相比的比值比为3.53。这项研究表明，GNB 3/C1429 T和LRP 5/A1330 V的组合是一个非常有用的标志物，用于预测一般日本人群中高胆固醇血症的发展。