BMI modifies associations of IL-6 genotypes with insulin resistance: The Framingham Study
BMI modifies associations of IL-6 genotypes with insulin resistance: The Framingham Study
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DOI：
10.1038/oby.2006.165
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发表时间：
2006-08-01
期刊：
影响因子：
6.9
通讯作者：
Cupples, L. Adrienne
中科院分区：
文献类型：
--
作者：
Herbert, Alan;Liu, Chunyu;Cupples, L. Adrienne
目的：- 174白介素(IL)-6基因多态性被认为是2型糖尿病的危险因素，但数据相互矛盾。由于白色脂肪是静息个体中IL-6的主要来源，我们验证了BMI改变IL-6基因型、胰岛素抵抗（IR）（使用稳态模型测量）和糖尿病风险之间关系的假设。研究方法和程序：对1991年至1995年参加Framingham后代研究的1525名成年人（平均年龄55.6岁，753名男性）进行社区队列研究，评估结果。结果：我们发现IL-6基因型和BMI对男性IR水平有显著的相互作用（p < 0.0001），其中C等位基因的肥胖纯合子最具抗性。在女性中，IL-6-BMI的相互作用不显著（p = 0.46）。在CC基因型男性中，BMI增加与糖尿病患病率增加相关[BMI每单位增加的优势比（OR）为1.30；95%可信区间（CI）， 1.11至1.50]，但GG （OR, 1.10; 95% Cl， 0.98至1.22）或GC基因型（OR, 1.05; 95% Cl， 0.97至1.14）的患者不存在这种情况。讨论：- 174 IL-6启动子多态性改变了男性肥胖与IR和糖尿病风险的关系。针对降低糖尿病风险的减肥方案可能对具有- 174 IL-6 CC基因型的男性特别有益。
Objective: The - 174 interleukin (IL)-6 gene polymorphism has been proposed as a risk factor for type 2 diabetes, but data are conflicting. Because white fat is a major source of IL-6 in resting individuals, we tested the hypothesis that BMI modifies the association among the IL-6 genotype, insulin resistance (IR) (measured using the homeostasis model), and risk of diabetes.Research Methods and Procedures: Outcomes were assessed in a community-based cohort study of 1525 adults (mean age, 55.6 years; 753 men), who participated in the Framingham Offspring Study during the 1991 to 1995 examinations.Results: We found a significant interaction between IL-6 genotype and BMI on levels of IR in men (p < 0.0001), with obese homozygotes for the minor C allele being most resistant. The IL-6-BMI interaction was not significant (p = 0.46) in women. Among men with the CC genotype, increasing BMI was associated with increased prevalence of diabetes [odds ratio (OR) per unit increase in BMI, 1.30; 95% confidence interval (CI), 1.11 to 1.50] but not among those with the GG (OR, 1.10; 95% Cl, 0.98 to 1.22) or GC genotype (OR, 1.05; 95% Cl, 0.97 to 1.14).Discussion: The - 174 IL-6 promoter polymorphism modifies the association of obesity with IR and diabetes risk in men. Weight loss regimens targeted at reducing the risk of diabetes may be of particular benefit for men with a - 174 IL-6 CC genotype.