Rheumatology Division, Hôpital Ambroise Paré, 9 Avenue Charles de Gaulle, Boulogne 92100, France.
Ann Rheum Dis. 2013 Apr;72(4):608-13. doi: 10.1136/annrheumdis-2012-201783. Epub 2012 Aug 15.
A robust association between polymorphisms in the non-major histocompatibility complex gene ERAP1 and ankylosing spondylitis (AS) in several populations was recently identified. The aim of the current study was to determine the level of association of ERAP1 polymorphisms with spondyloarthritis (SpA) in French/Belgian populations with particular attention to genotype-phenotype correlations.
We studied 734 independent SpA cases and 632 controls from two European cohorts. Five single-nucleotide polymorphisms (SNPs), rs27044, rs17482078, rs10050860, rs30187 and rs2287987 were genotyped, and case-control association analyses were carried using PLINK 1.07 software. Linkage disequilibrium and haplotypes were estimated with Haploview. Analysis was first carried out in SpA as a whole group, and then separately in AS and non-radiographic SpA (non-AS) patients.
Consistent with previous studies conducted in AS, rs30187 was the most significantly associated SNP with SpA (p=0.008 in the French, and p=6.46×10(-4) in the Belgian cohorts). In the combined cohorts, this SNP was associated with both AS and non-AS (P(combined)= 3.9×10(-5) and P(combined)= 0.005, respectively). A similar trend was observed with other SNPs. The rs17482078/rs10050860/rs30187-CCT haplotype was significantly associated with increased risk of SpA in both cohorts (P(combined)= 9.08×10(-4)), including AS and non-AS (P(combined)=6.16×10(-4) and P(combined)=0.049, respectively), whereas the -TTC haplotype was associated with reduced risk of SpA, including AS and non-AS (P(combined)=2.36×10(-7), P(combined)= 5.69×10(-6) and P(combined)= 2.13×10(-4), respectively).
This is the first study to show an association between several polymorphisms located in ERAP1 and SpA as a whole. Our findings demonstrate consistent association of the same SNPs and haplotypes with both AS and non-AS subtypes of SpA.
最近在多个人群中发现非主要组织相容性复合体基因 ERAP1 的多态性与强直性脊柱炎（AS）之间存在很强的关联。本研究的目的是确定 ERAP1 多态性与法国/比利时人群中脊柱关节炎（SpA）的关联程度，特别关注基因型-表型相关性。
我们研究了来自两个欧洲队列的 734 例独立的 SpA 病例和 632 例对照。使用 PLINK 1.07 软件对 5 个单核苷酸多态性（SNP）rs27044、rs17482078、rs10050860、rs30187 和 rs2287987 进行了基因分型，并进行了病例对照关联分析。使用 Haploview 估计连锁不平衡和单倍型。首先在整个 SpA 组中进行分析，然后分别在 AS 和非放射学 SpA（非 AS）患者中进行分析。
与先前在 AS 中进行的研究一致，rs30187 是与 SpA 最显著相关的 SNP（法国队列的 p=0.008，比利时队列的 p=6.46×10(-4)）。在合并队列中，该 SNP 与 AS 和非 AS 均相关（P(combined)=3.9×10(-5)和 P(combined)=0.005）。其他 SNP 也观察到类似的趋势。rs17482078/rs10050860/rs30187-CCT 单倍型与两个队列中 SpA 的发病风险增加显著相关（P(combined)=9.08×10(-4)），包括 AS 和非 AS（P(combined)=6.16×10(-4)和 P(combined)=0.049），而-TTC 单倍型与 SpA 的发病风险降低相关，包括 AS 和非 AS（P(combined)=2.36×10(-7)，P(combined)=5.69×10(-6)和 P(combined)=2.13×10(-4)）。
这是第一项研究表明 ERAP1 中几个位于 ERAP1 中的多态性与 SpA 整体之间存在关联。我们的研究结果表明，相同的 SNP 和单倍型与 AS 和非 AS 两种 SpA 亚型均存在一致的关联。
