Brown Matthew A
Centre for Immunology and Cancer Research, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, QLD 4102, Australia.
Best Pract Res Clin Rheumatol. 2006 Jun;20(3):611-21. doi: 10.1016/j.berh.2006.03.005.
There is strong evidence from twin and family studies indicating that a substantial proportion of the heritability of susceptibility to ankylosing spondylitis (AS) and its clinical manifestations is encoded by non-major-histocompatibility-complex genes. Efforts to identify these genes have included genomewide linkage studies and candidate gene association studies. One region, the interleukin (IL)-1 gene complex on chromosome 2, has been repeatedly associated with AS in both Caucasians and Asians. It is likely that more than one gene in this complex is involved in AS, with the strongest evidence to date implicating IL-1A. Identifying the genes underlying other linkage regions has been difficult due to the lack of obvious candidates and the low power of most studies to date to identify genes of the small to moderate magnitude that are likely to be involved. The field is moving towards genomewide association analysis, involving much larger datasets of unrelated cases and controls. Early successes using this approach in other diseases indicates that it is likely to identify genes in common diseases like AS, but there remains the risk that the common-variant, common-disease hypothesis will not hold true in AS. Nonetheless, it is appropriate for the field to be cautiously optimistic that the next few years will bring great advances in our understanding of the genetics of this condition.
来自双胞胎和家族研究的有力证据表明，强直性脊柱炎（AS）易感性及其临床表现的很大一部分遗传度是由非主要组织相容性复合体基因编码的。识别这些基因的努力包括全基因组连锁研究和候选基因关联研究。一个区域，即2号染色体上的白细胞介素（IL）-1基因复合体，在白种人和亚洲人中都反复与AS相关。该复合体中可能不止一个基因参与AS，迄今为止最有力的证据表明是IL-1A。由于缺乏明显的候选基因以及迄今为止大多数研究识别可能涉及的中小效应基因的能力有限，识别其他连锁区域的潜在基因一直很困难。该领域正朝着全基因组关联分析发展，涉及规模大得多的非亲属病例和对照数据集。在其他疾病中使用这种方法的早期成功表明，它很可能识别出像AS这样的常见疾病中的基因，但仍然存在常见变异-常见疾病假说在AS中不成立的风险。尽管如此，该领域谨慎乐观是合适的，因为未来几年我们对这种疾病遗传学的理解将取得巨大进展。
