Protective effect of an ERAP1 haplotype in ankylosing spondylitis: investigating non-MHC genes in HLA-B27-positive individuals
Protective effect of an ERAP1 haplotype in ankylosing spondylitis: investigating non-MHC genes in HLA-B27-positive individuals
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DOI：
10.1093/rheumatology/ket269
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发表时间：
2013-12-01
期刊：
影响因子：
5.5
通讯作者：
Bruges-Armas, Jacome
中科院分区：
文献类型：
--
作者：
Bettencourt, Bruno Filipe;Rocha, Fabiana Leal;Bruges-Armas, Jacome
目标。最近发现非MHC基因与强直性脊柱炎的相关性。我们的目的是研究ERAP1、IL23R和TNFSF15区域与人类白细胞抗原B27阳性个体AS易感性和保护性的关系。共检测了200例无血缘关系的AS患者和559例健康无血缘关系的AS患者，均为HLAB27阳性。检测了IL23R(9个SNPs)、ERAP1(5个SNPs)和TNFSF15(6个SNPs)的20个单核苷酸多态(SNPs)。ERAP1 rs30187[优势比(OR)=1.5，P=4.7×10(-3)]与AS易感性相关最强。Rs17482078(OR=0.7，P=2.8×10(-2))、rs10050860(OR=0.7，P=2.3×10(-2))、rs2287987(OR=0.6，P=1.3×10(-2))具有保护作用。ERAP1单倍型rs17482078/rs10050860/rs30187/rs2287987-CCTT与AS易感性相关(P=6.8×10(-3))，rs17482078/rs10050860/rs30187/rs2287987-TTCC具有保护作用(P=3.1×10(-2))。1个IL23R标记与AS易感性显著相关(rs1004819，P=4.3×10(-2)，OR=1.3)。在TNFSF15区域没有观察到关联。ERAP1中一个新的保护性单倍型的发现和TNFSF15区域的缺失可以为理解AS的易感性和保护机制提供新的见解。
Objective. The association of non-MHC genes with AS has been recently suggested. We aimed to investigate the association of the ERAP1, IL23R and TNFSF15 regions and the susceptibility to and protection from AS in HLA-B27-positive individuals.Methods. A total of 200 unrelated AS patients and 559 healthy unrelated subjects, all HLA-B27 positive, were tested. Twenty single nucleotide polymorphisms (SNPs) were investigated in and near IL23R (nine SNPs), in ERAP1 (five SNPs) and in TNFSF15 (six SNPs).Results. ERAP1 rs30187 [odds ratio (OR) = 1.5, P = 4.7 x 10(-3)] had the strongest association with AS susceptibility. A protective effect was found in three of the ERAP1 SNPs: rs17482078 (OR = 0.7, P = 2.8 x 10(-2)), rs10050860 (OR = 0.7, P = 2.3 x 10(-2)), rs2287987 (OR = 0.6, P = 1.3 x 10(-2)). The ERAP1 haplotype rs17482078/rs10050860/rs30187/rs2287987-CCTT showed an association with AS susceptibility (P = 6.8 x 10(-3)) and a protective effect was identified in rs17482078/rs10050860/rs30187/rs2287987-TTCC (P = 3.1 x 10(-2)). Significant association with AS susceptibility was found in one IL23R marker (rs1004819, P = 4.3 x 10(-2), OR = 1.3). No associations were observed in the TNFSF15 region.Conclusion. The identification of a new protection haplotype in ERAP1 and the lack of association of the TNFSF15 region can provide new insights into the understanding of the mechanisms underlying the susceptibility to and protection from AS.