Investigating the genetic basis for ankylosing spondylitis. Linkage studies with the major histocompatibility complex region.

摘要: Objective. To assess the hypothesis that B27 or a gene(s) in close proximity (e.g., within near major histocompatibility complex [MHC]) represents disease-causing ankylosing spondylitis (AS) gene, and therefore contributes directly to pathogenesis of this disorder. Methods. MHC haplotypes were determined by both serologic molecular analyses 15 multiple-case AS families from Toronto Newfoundland. Segregation with these was examined linkage identity-by-descent analyses. Attributable risk estimates for various genetic markers sex calculated. Results. Linkage established significant between MHC, maximal logarithm odds (LOD) score being 3.48 at recombination frequency (θ) 0.05. In second analysis which population association gene HLA—B27 taken into account, LOD 7.5 θ = Identity-by-descent showed departure random segregation among affected avuncular (P < 0.05) cousin 0.01) pairs. The presence HLA—B40 positive individuals increased disease more than 3-fold, confirming previous reports. Disease susceptibility modeling suggested an autosomal dominant pattern inheritance, penetrance approximately 20%. Conclusion. These data provide first conclusive demonstration region AS, confirm genes contribute AS.