Interleukin-6 genetic variability and adiposity: Associations in two prospective cohorts and systematic review in 26,944 individuals
Interleukin-6 genetic variability and adiposity: Associations in two prospective cohorts and systematic review in 26,944 individuals
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DOI：
10.1210/jc.2007-0877
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发表时间：
2007-09-01
影响因子：
5.8
通讯作者：
Hu, Frank B.
中科院分区：
文献类型：
--
作者：
Qi, Lu;Zhang, Cuilin;Hu, Frank B.
内容：IL-6（IL-6）是一种与肥胖相关的免疫调节细胞因子。目的：探讨IL-6基因的遗传变异与肥胖及长期变化的关系。设计和研究对象：我们检测了2255名健康女性和980名健康男性IL-6基因的连锁不平衡标记单核苷酸多态性。我们还对-174G > C多态性与结果：IL 6单倍型222211（具有rs 2069827、rs 1800797、rs 1800795、rs 1554606、rs 2069861和rs 1818879; 1个编码常见等位基因，2个编码次要等位基因）与较大腰围一致且显著相关（男性P = 0.009;女性P = 0.0003）和基线体重指数（BMI）（男性P = 0.01;女性P = 0.046）与最常见的单倍型111112进行比较。单倍型222211也与女性成年早期BMI显著较高相关（P = 0.007）。单体型相关的BMI差异在随访期间持续存在。5'启动子多态性rs 2069827始终与男性（携带者与非携带者，P = 0.01，0.007和0.008）和女性（P = 0.01，0.10和0.0016）中显著较高的成年早期BMI，基线BMI和腰围相关。从这项研究的数据和荟萃分析的26,944个人不支持最好的研究多态性，= 174 G> C，和adiposity.Conclusions：我们的数据从两个独立的队列表明，IL 6基因的变异性与肥胖症显着相关。这种关联不太可能由多态性-174G > C引起。
Context: IL-6 (IL6) is an immune-modulating cytokine associated with obesity in humans.Objective: Our objective was to assess the associations between the genetic variability of IL6 gene and adiposity and long-term changes.Design and Subjects: We determined the linkage disequilibrium-tagging single-nucleotide polymorphisms of IL6 gene in 2255 healthy women and 980 healthy men from two prospective cohorts. We also conducted a metaanalysis on the associations between polymorphism -174G > C (rs1800795) and adiposity.Results: IL6 haplotype 222211 ( possessing rs2069827, rs1800797, rs1800795, rs1554606, rs2069861, and rs1818879; 1 codes the common and 2 codes the minor alleles) was consistently and significantly associated with greater waist circumference (P = 0.009 in men; P = 0.0003 in women) and baseline body mass index ( BMI) ( P = 0.01 in men; P = 0.046 in women) compared with the most common haplotype 111112. Haplotype 222211 was also associated with significantly higher early-adulthood BMI in women ( P = 0.007). The haplotypeassociated difference in BMI persisted significantly during the follow-up. A 5' promoter polymorphism, rs2069827, was consistently associated with significantly higher early-adulthood BMI, baseline BMI, and waist circumference in men (carriers vs. noncarriers, P = 0.01, 0.007, and 0.008) and women ( P = 0.01, 0.10, and 0.0016). The data from this study and a metaanalysis of 26,944 individuals did not support substantial relations between the best-studied polymorphism, = 174G > C, and adiposity.Conclusions: Our data from two independent cohorts indicate that the variability of the IL6 gene is significantly associated with adiposity. Such associations are less likely to be caused by polymorphism -174G > C.