Virginia Commonwealth University, Richmond, VA 23298-0263, USA.
Osteoarthritis Cartilage. 2010 Feb;18(2):200-7. doi: 10.1016/j.joca.2009.08.006. Epub 2009 Sep 1.
Several research groups have examined osteoarthritis (OA) association with Interleukin-1 (IL-1) region markers and haplotypes. The results have been suggestive for hand OA, negative for knee OA, and conflicting for hip OA.
Our aim was to address conflicts employing meta-analytical methods on data from 1238 European-descent cases with various OA phenotypes and 1269 European-descent controls from four study centers. We imputed some missing genotype data and reconstructed IL-1 region extended haplotypes. A previously reported 7-marker IL1A-IL1B-IL1RN extended risk haplotype was tested for association with each specific index phenotype.
For hip OA, data from three centers showed heterogeneity of extended-risk-haplotype effect, two panels showing trend toward risk and another showing protection, with overall odds ratio (OR) 1.24 (95% Confidence interval (CI) 0.45-3.41, P 0.67). The heterogeneity fell partly along control ascertainment lines, chiefly between controls ascertained as spouses of arthroplasty patients and controls identified through population radiographic survey. For knee OA, the results showed no heterogeneity and no significant extended-risk-haplotype effect. For hand OA, the results showed little heterogeneity and a modest trend toward positive association (summary OR 1.34, 95% CI 0.83-2.17 P 0.23). Using a Bayesian partition modeling approach, the 7-marker extended haplotypes showed no significant effect on any OA phenotype examined. A 3-single-nucleotide polymorphism (SNP) IL1B-IL1RN haplotype rs1143627-rs16944-rs419598 showed a trend toward hand OA association (posterior probability of association 0.72) with the most prominent feature being protection from a specific haplotype representing a partial mirror image of the extended risk haplotype (OR estimated at 0.46).
The meta-analysis data do not confirm but only suggest that some hand and hip OA risk could be associated with the IL-1 region, particularly centered in IL1B and possibly also IL1RN.
有几个研究小组研究了骨关节炎（OA）与白细胞介素-1（IL-1）区域标记物和单倍型的关联。结果对手部 OA 有提示作用，对膝部 OA 则为阴性，对髋部 OA 则存在矛盾。
我们的目的是通过meta 分析方法，利用来自四个研究中心的 1238 名具有不同 OA 表型的欧洲裔病例和 1269 名欧洲裔对照者的数据来解决这些矛盾。我们对一些缺失的基因型数据进行了推断，并重建了 IL-1 区域扩展单倍型。先前报道的 7 个标记物 IL1A-IL1B-IL1RN 扩展风险单倍型与每个特定的指数表型进行了关联测试。
对于髋部 OA，来自三个中心的数据显示扩展风险单倍型效应存在异质性，两个面板显示出风险趋势，另一个面板显示出保护作用，总体比值比（OR）为 1.24（95%置信区间（CI）0.45-3.41，P 0.67）。异质性部分沿着对照者的确定线下降，主要是在通过人群放射学调查确定的对照者和作为关节置换术患者配偶确定的对照者之间。对于膝部 OA，结果显示没有异质性和没有显著的扩展风险单倍型效应。对于手部 OA，结果显示异质性较小，存在正向关联的趋势（汇总 OR 1.34，95% CI 0.83-2.17，P 0.23）。使用贝叶斯分区建模方法，7 个标记物的扩展单倍型对所检查的任何 OA 表型均无显著影响。3 个单核苷酸多态性（SNP）IL1B-IL1RN 单倍型 rs1143627-rs16944-rs419598 与手部 OA 关联呈趋势（关联后概率为 0.72），最显著的特征是对特定单倍型的保护，该单倍型代表扩展风险单倍型的部分镜像（估计 OR 为 0.46）。
荟萃分析数据不支持，但只是提示 IL-1 区域与手部和髋部 OA 风险有关，特别是集中在 IL1B 上，也可能在 IL1RN 上。
