Abstract
Ankylosing spondylitis (AS) is a chronic inflammatory disorder with a multifactorial genetic basis. HLA-B27 was reported with the greatest susceptibility to AS but did not act alone. The aim of this study was to search for other gene(s) associated with AS independently of HLA-B27 using 13 microsatellite markers spanning 1.5 Mb from locus TAP1 to HLA-Cw and a single-nucleotide polymorphism marker within NFkappaBIL1 gene promoter. Genotyping for microsatellites was performed in 175 AS patients of eastern Chinese and 219 ethnically matched healthy controls using polymerase chain reaction with fluorescence-labelled primers, whereas the SNP marker was genotyped by direct DNA sequencing. Allele as well as haplotype frequencies were compared between cases and controls, and a linkage disequilibrium analysis was performed to estimate the LD relationship between the candidate regions. The frequencies of alleles D6S2811*128, STR_MICA*A5.1 and D6S2672*109, as well as haplotypes D6S2811*128-D6S2927*213-D6S2810*340, D6S2927* 221-D6S2810*350-MICA*A5.1, and D6S2810*350-MICA*A5.1-D6S2800* 136 were significantly increased in B27-positive AS patients when compared with B27-positive controls. The results indicated that there may be other gene(s) within the HLA region, especially around locus HLA-B or HLA-Cw, with susceptibility to AS independently of HLA-B27.
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