Kämäräinen Olli-Pekka, Solovieva Svetlana, Vehmas Tapio, Luoma Katariina, Riihimäki Hilkka, Ala-Kokko Leena, Männikkö Minna, Leino-Arjas Päivi
Collagen Research Unit, Biocenter and Department of Medical Biochemistry and Molecular Biology, University of Oulu, 90220 Oulu, Finland.
Arthritis Res Ther. 2008;10(1):R21. doi: 10.1186/ar2374. Epub 2008 Feb 8.
The objective of this study was to investigate the relationship of the IL-6 promoter variants G-597A, G-572C and G-174C (rs1800797, rs1800796 and rs1800795, respectively), which have been shown to affect both the transcription and secretion of IL-6, to symptomatic distal interphalangeal (DIP) osteoarthritis (OA).
A total of 535 women aged 45 to 63 years were included. Radiographs of both hands were taken and each DIP joint was evaluated (grade 0 to 4) for the presence of OA. Information on symptoms (pain, tenderness) in each joint was collected by using a self-administered questionnaire. Symptomatic DIP OA was defined by the presence of both radiographic findings of grade 2 or more and symptoms in at least two DIP joints, and symmetrical DIP OA by the presence of radiographic findings of grade 2 or more in at least one symmetrical pair of DIP joints. Common polymorphic loci in the IL-6 gene were amplified and the promoter haplotypes were reconstructed from genotype data with the PHASE program. Logistic regression analysis was used to examine the association between the IL-6 genotypes/diplotypes and the DIP OA outcome.
The G alleles of two promoter single nucleotide polymorphisms (SNPs) G-597A and G-174C were more common among the subjects with symptomatic DIP OA than among those with no disease (P = 0.020 and 0.024, corrected for multiple testing). In addition, the carriage of at least one G allele in these positions increased the risk of disease (P = 0.006 and P = 0.008, respectively). Carrying a haplotype with the G allele in all three promoter SNPs increased the risk of symptomatic DIP OA more than fourfold (odds ratio (OR) 4.45, P = 0.001). Carriage of the G-G diplotype indicated an increased risk of both symmetrical DIP OA (OR 1.52, 95% confidence interval 1.01 to 2.28) and symptomatic DIP OA (OR 3.67, 95% confidence interval 1.50 to 9.00).
The present study showed that the presence of G alleles at common IL-6 polymorphic promoter loci was associated with the more severe DIP OA outcomes, symmetrical and symptomatic.
本研究的目的是调查白细胞介素6（IL-6）启动子变体G-597A、G-572C和G-174C（分别为rs1800797、rs1800796和rs1800795）与有症状的远端指间关节（DIP）骨关节炎（OA）之间的关系，这些变体已被证明会影响IL-6的转录和分泌。
共纳入535名年龄在45至63岁之间的女性。拍摄双手的X线片，并对每个DIP关节进行OA评估（0至4级）。通过自行填写问卷收集每个关节的症状（疼痛、压痛）信息。有症状的DIP OA定义为存在2级或更高的X线表现且至少两个DIP关节有症状，对称性DIP OA定义为至少一对对称的DIP关节存在2级或更高的X线表现。扩增IL-6基因中的常见多态性位点，并使用PHASE程序从基因型数据重建启动子单倍型。采用逻辑回归分析来检验IL-6基因型/双倍型与DIP OA结局之间的关联。
两个启动子单核苷酸多态性（SNP）G-597A和G-174C的G等位基因在有症状的DIP OA患者中比在无疾病患者中更常见（经多重检验校正后，P = 0.020和0.024）。此外，这些位置携带至少一个G等位基因会增加患病风险（分别为P = 0.006和P = 0.008）。在所有三个启动子SNP中携带含有G等位基因的单倍型会使有症状的DIP OA风险增加四倍多（优势比（OR）4.45，P = 0.001）。携带G-G双倍型表明对称性DIP OA（OR 1.52，95%置信区间1.01至2.28）和有症状的DIP OA（OR 3.67，95%置信区间1.50至9.00）的风险均增加。
本研究表明，IL-6常见多态性启动子位点存在G等位基因与更严重的DIP OA结局（对称性和有症状）相关。
