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The genetic basis of ankylosing spondylitis.

PURPOSE OF REVIEW: Genetic factors provide over 90% of the overall susceptibility to ankylosing spondylitis, with about half of the genetic contribution attributed to HLA-B27 and other major histocompatibility complex genes. Recent studies have focused on non-major histocompatibility complex genes. This review is aimed at summarizing the status of major histocompatibility complex and non-major histocompatibility complex genes in ankylosing spondylitis susceptibility, and suggests areas for future studies.

RECENT FINDINGS: A recent meta-analysis of published scans of ankylosing spondylitis susceptibility has confirmed sites on chromosomes 3q, 6p (the major histocompatibility complex), 10q, 16q and 19q in ankylosing spondylitis susceptibility. Non-major histocompatibility complex candidate gene analyses have confirmed a role for the IL-1 gene complex. The search for other non-major histocompatibility complex candidate genes, however, has been complicated by inadequate power in most previous studies. Innovations in genetic methodologies will allow thorough genome wide linkage disequilibrium mapping studies in large cohorts of patients that will result in the dissection of the genetic susceptibility to ankylosing spondylitis.

SUMMARY: Nearly half of the susceptibility to ankylosing spondylitis is provided by major histocompatibility complex genes. Non-major histocompatibility complex genes, most notably the IL-1 gene complex, have been identified and novel technologies promise that a more thorough examination of the rest of the genome will soon elucidate the genetic basis of this disease.

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