Khan Muhammad A, Ball Edward J
Department of Medicine, Division of Rheumatology, Case Western Reserve University School of Medicine, MetroHealth Medical Center, Cleveland, Ohio, USA.
Best Pract Res Clin Rheumatol. 2002 Sep;16(4):675-90.
There is substantial evidence strongly favouring a direct role for HLA-B27 in genetic susceptibility to ankylosing spondylitis (AS) and related spondyloarthropathies (SpA), although the underlying molecular basis has yet to be identified. HLA-B27 itself is a serologic specificity that encompasses 26 different alleles that encode 24 different subtypes - HLA-B2701 to B2725, with the exclusion of B2722. [The B2722 allele was deleted as an official WHO allele in April 2002, with a note that the reference cell has been shown to have the same sequence as B2706. Thus, from now on, with this deletion of B2722, there will be a "hole" among the HLA-B2701 to B2725 group of alleles]. The 24 HLA-B27 alleles (subtypes) seem to have evolved from the most widespread subtype, B2705. Two B27 alleles have been reported to lack association with AS: B2706 among Southeast Asian populations, and B*2709 among Sardinians. The distinction between the disease-associated subtypes and those that are not disease-associated may provide some clues to the actual role of HLA-B27 in disease pathogenesis. Genetic family studies in populations of European descent indicate that HLA-B27 contributes only 16 % of the total genetic risk for the disease. The genes in the Major Histocompatibility Complex (MHC) as a whole, that includes HLA-B27, account for about half of the genetic susceptibility for AS. This clearly indicates the presence of additional disease predisposing genes in the MHC region on chromosome 6, and genome-wide studies have identified many areas of interest on other chromosomes that may contain additional disease predisposing genes. Additional studies emanating from the recent mapping of the human genome is expected to lead to better understanding of the genetic basis of these and other rheumatic diseases. Genetic counselling and the use of HLA-B27 typing as an aid to diagnosis are also reviewed.
有大量证据强烈支持HLA - B27在强直性脊柱炎（AS）及相关脊柱关节病（SpA）的遗传易感性中起直接作用，尽管其潜在分子基础尚未明确。HLA - B27本身是一种血清学特异性，包含26个不同等位基因，编码24种不同亚型——HLA - B2701至B2725，但不包括B2722。[B2722等位基因于2002年4月被世界卫生组织从官方等位基因中删除，附注表明参考细胞的序列已被证明与B2706相同。因此，从现在起，随着B2722的删除，在HLA - B2701至B2725等位基因组中会出现一个“空缺”]。这24个HLA - B27等位基因（亚型）似乎是从分布最广的亚型B2705进化而来。据报道，有两个B27等位基因与AS无关：东南亚人群中的B2706和撒丁岛人中的B*2709。疾病相关亚型与非疾病相关亚型之间的差异可能为HLA - B27在疾病发病机制中的实际作用提供一些线索。对欧洲血统人群的遗传家系研究表明，HLA - B27仅占该疾病总遗传风险的16%。主要组织相容性复合体（MHC）中的基因整体，包括HLA - B27，约占AS遗传易感性的一半。这清楚地表明在6号染色体的MHC区域存在其他疾病易感基因，全基因组研究已经在其他染色体上确定了许多可能包含其他疾病易感基因的感兴趣区域。近期人类基因组图谱绘制所引发的更多研究有望增进对这些及其他风湿性疾病遗传基础的理解。本文还对遗传咨询以及使用HLA - B27分型辅助诊断进行了综述。
