Medical Research Council (MRC) Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Bristol, UK.
Nat Genet. 2011 Jul 10;43(8):761-7. doi: 10.1038/ng.873.
Ankylosing spondylitis is a common form of inflammatory arthritis predominantly affecting the spine and pelvis that occurs in approximately 5 out of 1,000 adults of European descent. Here we report the identification of three variants in the RUNX3, LTBR-TNFRSF1A and IL12B regions convincingly associated with ankylosing spondylitis (P < 5 × 10(-8) in the combined discovery and replication datasets) and a further four loci at PTGER4, TBKBP1, ANTXR2 and CARD9 that show strong association across all our datasets (P < 5 × 10(-6) overall, with support in each of the three datasets studied). We also show that polymorphisms of ERAP1, which encodes an endoplasmic reticulum aminopeptidase involved in peptide trimming before HLA class I presentation, only affect ankylosing spondylitis risk in HLA-B27-positive individuals. These findings provide strong evidence that HLA-B27 operates in ankylosing spondylitis through a mechanism involving aberrant processing of antigenic peptides.
强直性脊柱炎是一种常见的炎症性关节炎，主要影响脊柱和骨盆，在欧洲血统的成年人中，大约每 1000 人就有 5 人会患此病。在这里，我们报告了在 RUNX3、LTBR-TNFRSF1A 和 IL12B 区域中鉴定出的三个变体与强直性脊柱炎明显相关（在联合发现和复制数据集的组合中 P < 5 × 10(-8)），以及在 PTGER4、TBKBP1、ANTXR2 和 CARD9 中另外四个位点显示出在我们所有数据集之间强烈的关联（总体 P < 5 × 10(-6)，在三个研究数据集的每个数据集都得到支持）。我们还表明，编码内质网氨肽酶的 ERAP1 多态性，该酶参与 HLA Ⅰ类呈递前肽的修剪，仅影响 HLA-B27 阳性个体的强直性脊柱炎风险。这些发现提供了强有力的证据，表明 HLA-B27 通过涉及抗原肽异常处理的机制在强直性脊柱炎中起作用。
