Sims A-M, Timms A E, Bruges-Armas J, Burgos-Vargas R, Chou C-T, Doan T, Dowling A, Fialho R N, Gergely P, Gladman D D, Inman R, Kauppi M, Kaarela K, Laiho K, Maksymowych W, Pointon J J, Rahman P, Reveille J D, Sorrentino R, Tuomilehto J, Vargas-Alarcon G, Wordsworth B P, Xu H, Brown M A
Diamantina Institute of Cancer, Immunology and Metabolic Medicine, University of Queensland, Brisbane, Quensland, Australia.
Ann Rheum Dis. 2008 Sep;67(9):1305-9. doi: 10.1136/ard.2007.081364. Epub 2007 Dec 6.
The aim of the current study was to determine the contribution of interleukin (IL)1 gene cluster polymorphisms previously implicated in susceptibility for ankylosing spondylitis (AS) to AS susceptibility in different populations worldwide.
Nine polymorphisms in the IL1 gene cluster members IL1A (rs2856836, rs17561 and rs1894399), IL1B (rs16944), IL1F10 (rs3811058) and IL1RN (rs419598, the IL1RA VNTR, rs315952 and rs315951) were genotyped in 2675 AS cases and 2592 healthy controls recruited in 12 different centres in 10 countries. Association of variants with AS was tested by Mantel-Haenszel random effects analysis.
Strong association was observed with three single nucleotide polymorphisms (SNPs) in the IL1A gene (rs2856836, rs17561, rs1894399, p = 0.0036, 0.000019 and 0.0003, respectively). There was no evidence of significant heterogeneity of effects between centres, and no evidence of non-combinability of findings. The population attributable risk fraction of these variants in Caucasians is estimated at 4-6%.
This study confirms that IL1A is associated with susceptibility to AS. Association of the other IL1 gene complex members could not be excluded in specific populations. Prospective meta-analysis is a useful tool in confirmation studies of genes associated with complex genetic disorders such as AS, providing sufficiently large sample sizes to produce robust findings often not achieved in smaller individual cohorts.
本研究旨在确定先前与强直性脊柱炎（AS）易感性相关的白细胞介素（IL）-1基因簇多态性对全球不同人群AS易感性的影响。
对来自10个国家12个不同中心招募的2675例AS患者和2592例健康对照进行IL-1基因簇成员IL-1A（rs2856836、rs17561和rs1894399）、IL-1B（rs16944）、IL-1F10（rs3811058）和IL-1RN（rs419598、IL-1RA VNTR、rs315952和rs315951）的9种多态性基因分型。通过Mantel-Haenszel随机效应分析检测变异与AS的关联。
观察到IL-1A基因中的三个单核苷酸多态性（SNP）与AS有强关联（rs2856836、rs17561、rs1894399，p值分别为0.0036、0.000019和0.0003）。没有证据表明各中心之间存在显著的效应异质性，也没有证据表明研究结果不可合并。这些变异在白种人中的人群归因危险度估计为4%-6%。
本研究证实IL-1A与AS易感性相关。不能排除其他IL-1基因复合体成员在特定人群中的关联性。前瞻性荟萃分析是确认与AS等复杂遗传性疾病相关基因的研究中的一种有用工具，它能提供足够大的样本量以产生在较小的个体队列中通常无法获得的可靠结果。
