Association Of Human Leucocyte Antigen Complex With Ankylosing Spondylitis In Chinese Han Population

Ankylosing spondylitis (AS) is a chronic inflammatory disorder characterized by inflammation in the spine and sacroiliac joints causing initial bone and joint erosion and subsequent ankylosis. It is the second-most common cause of inflammatory arthritis worldwide, with a prevalence of 0.2-0.9 % in white populations and 0.26 % in Chinese population. The sibling recurrence risk ratio and twin studies suggested that strong genetic factors are implicated in the etiology of the disease.Human leukocyte antigen (HLA) complex, which encompasses 3.6 Mb on chromosome 6p21.3, is divided into three regions, class I, class II, and class III. Most genes in the HLA region are involed in regulating immune responses or inflammation. HLA was identified as the region with the greatest susceptibility to AS by three independent whole genome screen studies, and HLA-B27 has been reported as the major gene involved in susceptibility to AS since 1970s'. Several studies showed that there may be other genes associated with AS within the HLA region, such as HLA-B60, HLA-DR1, TNF-α, and MICA. So, it should be a worthwhile plan to search for genes which are associated with AS independently of HLA-B27 within the HLA region in Chinese Han population due to extent of linkage disequilibrium in this region and genetic heterogeneity in different ethnic groups.We performed a case-control study on 175 AS patients of eastern Chinese and 219 ethnically matched healthy controls using thirteen microsatellite markers spanning 1.5 Mb from locus TAP1 to HLA-Cw and a single nucleotide polymorphism marker within NFκBIL1 gene promoter. Genotyping for microsatellites was performed on ABI 3130 genetic analyzer using fluorescence microsatellite electrophoresis, whereas the SNP marker was genotyped by direct DNA sequencing. We found that 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 HLA-B27 positive AS patients when compared with HLA-B27 positive controls from single-locus analysis and 3-marker-sliding-window haplotype analysis.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.