Open AccessAssociation of the KIR3DS1*013 and KIR3DL1*004 alleles with susceptibility to ankylosing spondylitis
Author(s) -
DíazPeña Roberto,
VidalCastiñeira Jose Ramón,
AlonsoArias Rebeca,
SuarezAlvarez Beatriz,
Vicario Jose Luis,
Solana Rafael,
Collantes Eduardo,
LópezVázquez Antonio,
MartínezBorra Jesús,
LópezLarrea Carlos
Publication year - 2010
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.27332
Subject(s) - allele , ankylosing spondylitis , immunology , hla b antigens , odds ratio , allele frequency , medicine , human leukocyte antigen , biology , genetics , antigen , gene
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.