A genomewide scan for the susceptibility gene loci to ankylosing spondylitis in Chinese Han population

Ankylosing spondylitis (AS) is a common inflammatory arthritis,with a prevalence of 1‰～3‰ in Caucasian and 2‰ in Chinese population.The recognition of the association of HLA-B27 with AS confirmed the importance of heritable factors in the disease.Whole-genome scans showed that some affected-sibling-pair families with AS not only demonstrated strong linkage to the MHC locus,but also identified other regions with suggestive or stronger linkage on chromosomes 1p,2q,9q,10q,16q and 19q.In order to localize the regions containing genes that determine susceptibility to AS in Chinese Han population,a genomewide screen was performed in nine Chinese families with AS,including 29 affected individuals.LINKAGE and GENEHUNTER packages were used for parametric (LOD) and non-parametric (NPL) analysis.The significant two-point LOD score value with D6S276 (at 44.9 cM from the 6p terminal) was 3.8821 in parametric analysis.Fine mapping showed LOD scores of D6S1691(at 42.7 cM) and D6S1618 (at 47.6 cM) around D6S276 were 1.5717 and 2.0056,respectively.Single point NPL score of D6S276,D6S1691 and D6S1618 were 2.6053,2.7490,2.0202,respectively,and minimum P value were 0.0072,0.0047,and 0.0265,respectively.Using multipoint NPL,the maximum LOD score values,NPL score and minimum P value obtained near D6S276 were 5.0623,3.7561,and 0.000233,respectively.As a result,the strong linkage of the D6S276 with AS was found,the region of D6S1691-D6S276-D6S1618 existed a susceptibility gene of AS.In addition,the LOD scores of D3S1292,D4S1535 and D18S64 were larger than 1.0,so they might be some suggestive linkage markers with AS.