胰岛素诱导基因2基因多态性rs7566605与肥胖及血脂关系的10年纵向研究

Association of insulin-induced gene 2 gene rs7566605 polymorphism with obesity and lipids: a 10-year longitudinal study

摘要:

目的 探索不同基因遗传模型下，胰岛素诱导基因2（INSIG2）基因多态性rs7566605在中国老年人群中与肥胖及血脂代谢的关系。方法 纵向分析2001年和2010年参加并完成两次北京市老年人健康问卷调查、具有重复测量资料的742例样本。观察参与者体质量指数（BMI）、空腹血糖及血脂指标随年龄变化趋势及年龄因素对血脂代谢遗传效应的影响，并分析不同遗传模型下，rs7566605基因型与肥胖及血脂代谢异常疾病之间的关联。结果 10年间两组人群（男性及女性）除BMI值降低以外，空腹血糖，甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-C）及收缩压都有所增加；血清总胆固醇水平在男性人群中增加而在女性人群中降低；此外，2001年资料显示，带有C位点的男性血清空腹血糖及TG水平高于野生GG型，携带C等位基因女性HDL-C水平则表现为下降趋势。rs7566605基因多态性在4个遗传模型下均未发现与肥胖存在统计学关联。在显性及杂合共显性遗传模型下，rs7566605 C等位基因可增加低高密度脂蛋白胆固醇血症的患病风险（显性模型：P＝0.011，OR＝1.726；杂合共显性模型：P＝0.002，OR＝1.890），而对高胆固醇血症存在保护作用（显性模型：P＝0.008，OR＝0.601；加性模型：P＝0.040，OR＝0.753；杂合共显性模型：P＝0.015，OR＝0.634）。结论 在中国老年人群中，INSIG2基因上游基因多态性rs7566605 C等位基因与血清脂类代谢可能存在关联，显性或杂合共显性模型或为其主要遗传模式。

Abstract:

Objective To investigate the association of rs7566605 polymorphism in the insulin-induced gene 2 (INSIG2) with obesity and lipid metabolism in Chinese elderly. Methods A total of 742 elderly receiving 2 surveys conducted during the years of 2001 and 2010 were subjected and longitudinally analyzed. All participants were asked to complete the health questionnaires and genotyping. The changes in body mass index (BMI), fasting blood glucose and blood lipid levels between the twice examinations were observed. The effects of aging and genetics on lipid metabolism were analyzed in the cohort. Moreover, the association between the rs7566605 genotypes with obesity and dyslipidemia, including hypercholesterolemia, hypertriacylglycerolemia or low high-density lipoprotein cholesterol (HDL-C) was analyzed with a variety of genetic models. Results Besides BMI, serum levels of fasting blood glucose, triglycerides (TG), HDL-C and the value of systolic blood pressure were increased in both male and female subjects during the 10 years. Serum total cholesterol was increased in the males but decreased in the females. Based on the data of 2001, the serum levels of fasting blood glucose and TG were higher in the males with allele C than with GG, while the females with allele C had lower level of HDL-C. No association was found between the rs7566605 genotypes with obesity. Logistic regression analysis indicated that allele C increased the risk of lower HDL-C (dominant model: P＝0.011, OR＝1.726; heterogeneous codominant model: P＝0.002，OR＝1.890), while it showed a protective effect on hypercholesterolemia (dominant model: P＝0.008, OR＝0.601; additive model: P＝0.040, OR＝0.753; heterogeneous codominant model: P＝0.015, OR＝0.634). Conclusion INSIG2 gene rs7566605 polymorphic allele C is associated with serum lipid metabolism in Chinese elderly population. Dominant and heterogeneous codominant model might be main genetic models for the gene.