Qi Lu, van Dam Rob M, Meigs James B, Manson JoAnn E, Hunter David, Hu Frank B
Department of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA.
Hum Mol Genet. 2006 Jun 1;15(11):1914-20. doi: 10.1093/hmg/ddl113. Epub 2006 Apr 27.
Interleukin-6 (IL-6, gene symbol IL6) is a proinflammatory cytokine. High circulating IL-6 levels have been associated with insulin resistance and greater risk of type 2 diabetes. Using a linkage disequilibrium (LD)-based approach, we sought to investigate the associations of the common polymorphisms comprehensively defining the genetic variability at the IL6 locus with diabetes risk. We conducted a case-control study of 2691 cases of type 2 diabetes (1692 women and 999 men) and 3237 control subjects (2238 women and 999 men) from the Nurses' Health Study and the Health Professional Follow-up Study. Pairwise LD analysis indicated that all the IL6 polymorphisms (rs2069827, rs1800797, rs1800795, rs1554606, rs2069849, rs2069861 and rs1818879) were in strong LD. We did not find significant associations between IL6 polymorphisms and the risk of type 2 diabetes in women or men, individually or in haplotypes. In addition, none of the IL6 polymorphisms was significantly associated with the plasma levels of IL-6 in the control subjects. Our meta-analysis of 5383 diabetes case and 12 069 controls indicated a null association between the best-studied 5' promoter polymorphism--174G>C (rs1800795)--and diabetes risk. Diversity in adiposity, age and sex could not account for the heterogeneity across different studies. In summary, the data in this study do not support substantial associations between the common polymorphisms in IL6 gene and circulating IL-6 levels and the risk of type 2 diabetes.
白细胞介素-6（IL-6，基因符号IL6）是一种促炎细胞因子。循环中IL-6水平升高与胰岛素抵抗及2型糖尿病风险增加相关。我们采用基于连锁不平衡（LD）的方法，全面研究定义IL6基因座遗传变异性的常见多态性与糖尿病风险之间的关联。我们对来自护士健康研究和卫生专业人员随访研究的2691例2型糖尿病患者（1692名女性和999名男性）和3237名对照者（2238名女性和999名男性）进行了病例对照研究。成对LD分析表明，所有IL6多态性（rs2069827、rs1800797、rs1800795、rs1554606、rs2069849、rs2069861和rs1818879）均处于强LD状态。我们未发现IL6多态性与女性或男性2型糖尿病风险之间存在显著关联，无论是单独分析还是单倍型分析。此外，在对照者中，没有一种IL6多态性与IL-6的血浆水平显著相关。我们对5383例糖尿病病例和12069例对照者的荟萃分析表明，研究最多的5'启动子多态性——174G>C（rs1800795）——与糖尿病风险之间无关联。肥胖、年龄和性别的差异无法解释不同研究之间的异质性。总之，本研究数据不支持IL6基因常见多态性与循环IL-6水平及2型糖尿病风险之间存在实质性关联。
