Association of the KIR3DS1*013 and KIR3DL1*004 alleles with susceptibility to ankylosing spondylitis.
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.


CONCLUSIONS
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.
Hospital Universitario Central de Asturias, 33006-Oviedo, Spain.
Roberto
R
Díaz-Peña
Jose Ramón
JR
Vidal-Castiñeira
Rebeca
R
Alonso-Arias
Beatriz
B
Suarez-Alvarez
Jose Luis
JL
Vicario
Rafael
R
Solana
Eduardo
E
Collantes
Antonio
A
López-Vázquez
Jesús
J
Martínez-Borra
Carlos
C
López-Larrea
D000483:Alleles; D015331:Cohort Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D015235:HLA-B Antigens / Q000235:genetics; D006801:Humans; D016017:Odds Ratio; D016133:Polymerase Chain Reaction / Q000379:methods; D054341:Receptors, KIR3DL1 / Q000235:genetics*; D054349:Receptors, KIR3DS1 / Q000235:genetics*; D012016:Reference Values; D013167:Spondylitis, Ankylosing / Q000235:genetics*
D015235:HLA-B Antigens; C042388:HLA-Bw4 antigen; C515083:KIR3DL1 protein, human; D054341:Receptors, KIR3DL1; D054349:Receptors, KIR3DS1