Herbert Alan, Liu Chunyu, Karamohamed Samer, Liu Jun, Manning Alisa, Fox Caroline S, Meigs James B, Cupples L Adrienne
Department of Genetics and Genomics, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118, USA.
Obesity (Silver Spring). 2006 Aug;14(8):1454-61. doi: 10.1038/oby.2006.165.
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.
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.
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% CI, 0.98 to 1.22) or GC genotype (OR, 1.05; 95% CI, 0.97 to 1.14).
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.
白细胞介素（IL）-6基因-174位点多态性被认为是2型糖尿病的一个风险因素，但相关数据存在矛盾。由于在静息个体中白色脂肪是IL-6的主要来源，我们检验了以下假设：体重指数（BMI）可改变IL-6基因型、胰岛素抵抗（IR）（采用稳态模型测定）与糖尿病风险之间的关联。
在一项基于社区的队列研究中评估各项结果，该研究纳入了1525名成年人（平均年龄55.6岁；男性753名），他们在1991年至1995年的检查中参与了弗雷明汉后代研究。
我们发现男性中IL-6基因型与BMI在IR水平上存在显著交互作用（p<0.0001），携带次要C等位基因的肥胖纯合子胰岛素抵抗最强。女性中IL-6-BMI交互作用不显著（p = 0.46）。在CC基因型的男性中，BMI升高与糖尿病患病率增加相关[BMI每增加一个单位的比值比（OR）为1.30；95%置信区间（CI）为1.11至1.50]，但GG基因型（OR为1.10；95%CI为0.98至1.22）或GC基因型（OR为1.05；95%CI为0.97至1.14）的男性并非如此。
IL-6启动子-174位点多态性改变了男性肥胖与IR及糖尿病风险之间的关联。针对降低糖尿病风险的减重方案可能对携带IL-6 -174 CC基因型的男性特别有益。
