Association of the KIR3DS1*013 and KIR3DL1*004 Alleles With Susceptibility to Ankylosing Spondylitis
Association of the KIR3DS1*013 and KIR3DL1*004 Alleles With Susceptibility to Ankylosing Spondylitis
复制标题
DOI：
10.1002/art.27332
复制
发表时间：
2010-04-01
影响因子：
--
通讯作者：
Lopez-Larrea, Carlos
中科院分区：
文献类型：
--
作者：
Diaz-Pena, Roberto;Ramon Vidal-Castineira, Jose;Lopez-Larrea, Carlos
目标。杀伤细胞免疫球蛋白样受体（KIRs）形成一组特异性识别HLA I类分子的调节分子。本研究的目的是分析除HLA-B27外，KIR3DL1和KIR3DS1等位基因在西班牙人群中对强直性脊柱炎（AS）易感性的可能贡献。我们对2组AS患者和健康对照进行了KIR3DS1和KIR3DL1等位基因分型。共有270名AS患者和435名来自西班牙的健康、hla - b27阳性匹配对照受试者入组。采用序列特异性寡核苷酸探针聚合酶链反应对KIR3DS1和KIR3DL1等位基因进行分型，并分析其与AS的相关性。所有个体均进行hla - b型分型。与健康的hla - b27阳性对照相比，AS患者中KIR3DS1*013等位基因是激活剂受体KIR3DS1频率增加的唯一原因（35.7%对22.6% [P = 10(-6)]，优势比1.90,95%置信区间1.50-2.40）。AS患者中KIR3DS1*013等位基因频率的增加与HLA-Bw4I80表位的存在与否无关。此外，空等位基因KIR3DL1*004是一种独特的抑制KIR3DL1等位基因，在hla - bw4i80存在时与AS呈负相关。在AS患者中，KIR3DS1*013等位基因的频率增加显然与HLA-Bw4I80表位的存在无关，而在HLA-Bw4I80表位存在时，KIR3DL1*004等抑制性等位基因的存在与AS患者呈负相关。因此，KIR基因型对As易感性的影响可能是由保护性/抑制性和风险/激活性同种异体之间的普遍不平衡介导的。
Objective. The killer cell immunoglobulin-like receptors (KIRs) form a group of regulatory molecules that specifically recognize HLA class I molecules. The aim of this study was to analyze the possible contribution of the KIR3DL1 and KIR3DS1 alleles, in addition to HLA-B27, in the susceptibility to ankylosing spondylitis (AS) in a population of individuals from Spain.Methods. We genotyped the KIR3DS1 and KIR3DL1 alleles in 2 cohorts of patients with AS and healthy control subjects. In total, 270 patients with AS and 435 healthy, HLA-B27-positive matched control subjects from Spain were enrolled. The KIR3DS1 and KIR3DL1 alleles were genotyped by sequence-specific oligonucleotide probe-polymerase chain reaction, and their association with AS was analyzed. All individuals were typed for HLA-B.Results. The KIR3DS1*013 allele was solely responsible for the increased frequency of the activator receptor KIR3DS1 in patients with AS compared with healthy HLA-B27-positive control subjects (35.7% versus 22.6% [P = 10(-6)], odds ratio 1.90, 95% confidence interval 1.50-2.40). The increased frequency of the KIR3DS1*013 allele in patients with AS was independent of the presence or absence of the HLA-Bw4I80 epitope. Moreover, the null allele KIR3DL1*004 was a unique inhibitory KIR3DL1 allele that showed a negative association with AS in the presence of HLA-Bw4I80.Conclusion. The increased frequency of the KIR3DS1*013 allele in patients with AS is clearly independent of the presence of the HLA-Bw4I80 epitope, whereas the presence of inhibitory allotypes such as KIR3DL1*004 demonstrated a negative association in patients with AS in the presence of HLA-Bw4I80. As a consequence, the influence of KIR genotypes on AS susceptibility would be mediated by a general imbalance between protective/inhibitory and risk/activating allotypes.