Maksymowych Walter P, Rahman Proton, Reeve Jeff P, Gladman Dafna D, Peddle Lynette, Inman Robert D
University of Alberta, Edmonton, Alberta, Canada.
Arthritis Rheum. 2006 Mar;54(3):974-85. doi: 10.1002/art.21642.
To examine the association between the IL1 gene cluster and susceptibility to ankylosing spondylitis (AS) in 3 independent case-control cohorts.
We analyzed 394 patients and 446 controls from Alberta, Newfoundland, and Toronto, Canada. Samples were genotyped using a panel of 38 single-nucleotide polymorphism (SNP) markers within the IL1 gene cluster. Data from 20 informative and nonredundant SNP markers were analyzed using several association test strategies. First, we used the program WHAP to identify single-marker associations. Second, we used WHAP to analyze "sliding windows" of 3 contiguous markers along the entire extent of the IL1 gene cluster in order to identify haplotypic associations. Third, we used the linkage disequilibrium mapping program DMLE to estimate the posterior probability distribution of a disease locus.
A total of 14 SNP markers showed significant single-locus disease associations, the most significant being rs3783526 (IL1A) (P = 0.0009 in the Alberta cohort, P = 0.04 in the Newfoundland cohort) and rs1143627 (IL1B) (P = 0.0005 in the Alberta cohort, P = 0.02 in the Newfoundland cohort). Analysis of 3-marker sliding windows revealed significant and consistent associations with all of the haplotypes in the IL1A and IL1B loci in the Alberta cohort and with IL1B in the Newfoundland cohort, especially haplotypes rs1143634/rs1143630/rs3917356 and rs1143630/rs3917356/rs3917354 (P = 0.006-0.0001). With DMLE, a strong peak in the probability distribution was estimated near IL1A in both the Alberta and the Newfoundland populations.
These results indicate that the IL1 locus, or a locus close to IL1, is associated with susceptibility to AS.
在3个独立的病例对照队列中研究白细胞介素1（IL1）基因簇与强直性脊柱炎（AS）易感性之间的关联。
我们分析了来自加拿大艾伯塔省、纽芬兰和多伦多的394例患者及446例对照。使用IL1基因簇内的一组38个单核苷酸多态性（SNP）标记对样本进行基因分型。使用几种关联测试策略分析了来自20个信息丰富且无冗余的SNP标记的数据。首先，我们使用WHAP程序来识别单标记关联。其次，我们使用WHAP分析沿着IL1基因簇全长的3个相邻标记的“滑动窗口”，以识别单倍型关联。第三，我们使用连锁不平衡定位程序DMLE来估计疾病位点的后验概率分布。
共有14个SNP标记显示出显著的单基因座疾病关联，最显著的是rs3783526（IL1A）（在艾伯塔队列中P = 0.0009，在纽芬兰队列中P = 0.04）和rs1143627（IL1B）（在艾伯塔队列中P = 0.0005，在纽芬兰队列中P = 0.02）。对3标记滑动窗口的分析显示，在艾伯塔队列中与IL1A和IL1B基因座中的所有单倍型以及在纽芬兰队列中与IL1B存在显著且一致的关联，尤其是单倍型rs1143634/rs1143630/rs3917356和rs1143630/rs3917356/rs3917354（P = 0.006 - 0.0001）。使用DMLE，在艾伯塔和纽芬兰人群中均估计在IL1A附近的概率分布出现一个强峰。
这些结果表明IL1基因座或与IL1接近的一个基因座与AS易感性相关。
