Department of Twin Research, St. Thomas' Hospital Campus, Kings College London School of Medicine London, UK.
Osteoarthritis Cartilage. 2010 May;18(5):699-704. doi: 10.1016/j.joca.2009.12.012. Epub 2010 Feb 6.
Interleukin-6 is a pro-inflammatory cytokine involved in the pathogenesis of osteoarthritis (OA). We investigated the role of two single nucleotide polymorphisms (SNPs) mapping to the promoter of the IL-6 gene on genetic susceptibility to hip and knee OA.
The -174G/C (rs1800795) and -597G/A (rs1800797) SNPs, implicated in the literature in risk of hip and hand OA, were genotyped in 2511 controls, 1101 hip OA cases and 1904 knee OA cases from four cohorts from the UK and Estonia. Data were analysed in conjuntion with published data on rs1800797 from the Genetics of OA and Lifestyle study (UK) on 791 controls, 1034 knee and 997 hip OA cases and rs1800795 data on 75 hip OA cases and 96 controls from Italy. Cases included both radiographic OA only and radiographic and symptomatic OA. Fixed and random-effects meta-analysis models were tested.
No significant association was found with hip OA or knee OA with either SNP nor with the haplotypes formed by them. For individual SNPs the smallest P-value for hip OA was observed using a random-effects model for rs1800795 OR(Gallele)=1.066 (95% CI 0.89-1.28) P<0.49, and significant heterogeneity between cohorts (I(2)=65%, P<0.034) was detected. For knee OA the smallest P-value was seen for rs1800797 OR(Aallele)=1.055 (95%CI 0.98-1.12) P<0.18, no significant heterogeneity was observed (I(2)=0%, P<0.68).
Our data do not support a role for the -174 and -597 IL-6 promoter polymorphisms in genetic susceptibility to knee or hip OA in Caucasian populations.
白细胞介素-6 是一种促炎细胞因子，参与骨关节炎（OA）的发病机制。我们研究了两个单核苷酸多态性（SNP）在 IL-6 基因启动子上的定位与髋和膝 OA 遗传易感性的关系。
在来自英国和爱沙尼亚的四个队列的 2511 名对照、1101 髋 OA 病例和 1904 膝 OA 病例中，对文献中与髋和手部 OA 风险相关的 -174G/C(rs1800795)和-597G/A(rs1800797)SNP 进行了基因分型。对英国遗传学和生活方式研究（英国）中 791 名对照、1034 膝和 997 髋 OA 病例的 rs1800797 数据以及意大利的 75 髋 OA 病例和 96 名对照的 rs1800795 数据进行了分析。病例包括仅影像学 OA 和影像学和症状性 OA。测试了固定和随机效应荟萃分析模型。
与髋 OA 或膝 OA 相比，两个 SNP 及其形成的单倍型均无显著相关性。对于个体 SNP，使用随机效应模型观察到髋 OA 的最小 P 值为 rs1800795 OR(Gallele)=1.066(95%CI0.89-1.28)P<0.49，并且检测到队列之间存在显著的异质性（I(2)=65%，P<0.034）。对于膝 OA，观察到最小的 P 值为 rs1800797OR(Aallele)=1.055(95%CI0.98-1.12)P<0.18，未观察到显著的异质性（I(2)=0%，P<0.68）。
我们的数据不支持 -174 和 -597 IL-6 启动子多态性在白种人群中与髋或膝 OA 遗传易感性有关。
