HLA-A2402 and a microsatellite (D6S248) are secondary independent susceptibility markers to ankylosing spondylitis in basque patients

Ankylosing spondylitis (AS) is universally associated with human leukocyte antigen B27 (HLA-B27), although other genes could determine the development and clinical expression of the disease. HLA-A9 (A*2402) allele was previously found to be associated in Basque patients. The objective of this study is to perform a more precise analysis of microsatellite polymorphisms in HLA-A*2402 and B27 haplotypes to elucidate the significance of this association. A group of 50 unrelated AS patients and 113 controls of Basque origin were studied. Eight microsatellites in the class I major histocompatibility complex region with vicinity to HLA-A and -B were analyzed and the strength of allelic associations to AS and linkage disequilibrium (LD) between alleles were evaluated. Allele 15 at the microsatellite locus D6S248, 1000Kb telomeric to HLA-A showed a strong positive association with the disease( OR:6; p c = 4.7×10 −4) and it could not be explained by LD to HLA-B27, HLA-A*2402 or any other loci. We found that D6S248-15 allele together with HLA-A*2402 could be B27-independent markers of additional susceptibility gene/s localised in the region telomeric to HLA-A in Basque AS patients.