HLA‐A*9, a probable secondary susceptibility marker to ankylosing spondylitis in Basque patients

Abstract

HLA-B27 is strongly associated to ankylosing spondylitis (AS). The objective of our study was to analyze HLA-B27 association, B27 subtype distribution and frequency of other HLA class I and DR antigens in a group of Basque AS patients. HLA class I antigens were typed serologically and HLA-B27 and A9 subtypes were determined by DNA typing in samples from 46 patients with AS, 54 B27-positive spondyloarthropathies, 82 healthy subjects and 20 B27-positive controls. A class I HLA 9.2 kb PvuII restriction fragment length polymorphism (RFLP), previously associated with AS, was analyzed in a representative group of patients and controls. We found that HLA-B*2705 conferred a relative risk of 126 for AS in this group. HLA-A9 (A*2402) allele was significantly increased in AS patients compared with healthy controls and B27-positive control group (Pcorr<0.0001) and also increased in patients affected with peripheral arthritis. No association between class I HLA 9.2 Kb RFLP and AS was found. These results suggest that HLA-A*9 allele itself or another linked gene could act as a secondary and independent susceptibility allele to AS.

HLA-A*2402 and a microsatellite (D6S248) are secondary independent susceptibility markers to ankylosing spondylitis in basque patients

“…The data reported in our previous study [7] supported the dominant role of HLA-B27 in the pathogenesis of AS also in the Basque population although we found a significant high increase of HLA-A9 and its split A*24(A*2402) in the group of AS patients independently of HLA-B27. Now, the analysis of microsatellites frequencies showed a relevant association of AS disease to D6S248-15 microsatellite allele and again, no significant LD between this allele and HLA-B27 could be demonstrated (Table 3).…”

“…Only a few studies have connected HLA-A locus and AS susceptibility: Mehra et al found a significant association between HLA-A9 and acute anterior uveitis in Indian AS patients and Reveille et al reported HLA-A24 frequency marginally increased in AS patients with peripheral arthritis but these results were not confirmed in other studies carried out later (reviewed in [7]). Our results put forward a HLA-B27-independent association of HLA-A9 (A*2402) to AS in this group of Basque patients.…”

“…They are localized in class I region between D6S273, 400-to 450-kb centromeric to HLA-B to D6S276, 6-Mb telomeric to HLA-A ( Figure 1). They were selected due to its proximity to HLA-B and HLA-A, both loci probably related with AS in our population [7]. Their localization, characteristics, and primers for polymerase chain reaction (PCR) were extracted mainly from [9] and NIH database, online at http://www.ncbi.nlm.nih.gov/.…”

“…A previous study [7] showed that HLA-B*2705, the only subtype found, conferred a risk of 126 for AS in a group of Basque patients. Interestingly, an independent association of HLA-A*2402 allele was found among this group when compared with controls (p c ϭ 1.71ϫ10 Ϫ3 ; relative risk [RR] ϭ 7.45) and also when compared with HLA-B27 positive controls (p c ϭ 2ϫ10 Ϫ2 ; RR ϭ 10.3).…”

Effect of HLA-B and HLA-DR genes on susceptibility to and severity of spondyloarthropathies in Mexican patients

“…Thus several groups have reported DR1, 7 DR4, 8 B60, 9 and A9 (A*2402) 10 associations with AS and a contradictory association with DR8. 11 Apart from HLA-B27, 12 13 particularly B*2705, 14 AS and other SpA in Mexicans have been associated with HLA-B39, FC31, DR8, and LMP2.…”