Genetic aspects of ankylosing spondylitis
Genetic aspects of ankylosing spondylitis
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DOI：
10.1053/berh.2002.0243
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发表时间：
2002-09-01
影响因子：
5.2
通讯作者：
Ball, EJ
中科院分区：
文献类型：
--
作者：
Khan, MA;Ball, EJ
有大量证据强烈支持HLA-B27在强直性脊柱炎（AS）和相关脊柱关节病（SPA）的遗传易感性中的直接作用，尽管潜在的分子基础尚未确定。HLA-B27本身是一种血清学特异性，包括编码24种不同亚型的26种不同等位基因-HLA-B *2701至B*2725，不包括B*2722。[The B*2722等位基因在2002年4月作为正式的WHO等位基因被删除，注意到参考细胞已显示具有与B*2706相同的序列。因此，从现在开始，随着B*2722的这种缺失，在HLA-B *2701至B*2725组等位基因之间将存在“洞”。24个HLA-B27等位基因（亚型）似乎是从最广泛的亚型B*2705进化而来的。据报道，有两个B27等位基因与AS缺乏关联：东南亚人群中的B*2706，撒丁岛人群中的B*2709。疾病相关亚型和非疾病相关亚型之间的区别可能为HLA-B27在疾病发病机制中的实际作用提供一些线索。欧洲血统人群的遗传家族研究表明，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，包括HLA-B27，占AS遗传易感性的一半左右。这清楚地表明在6号染色体上的MHC区域中存在额外的疾病易感基因，并且全基因组研究已经确定了其他染色体上可能含有额外疾病易感基因的许多感兴趣区域。从最近人类基因组图谱中产生的其他研究预计将导致更好地了解这些和其他风湿性疾病的遗传基础。遗传咨询和使用HLA-B27分型作为辅助诊断也进行了审查。
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-B*2701 to B*2725, with the exclusion of B*2722. [The B*2722 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 B*2706. Thus, from now on, with this deletion of B*2722, there will be a "hole" among the HLA-B*2701 to B*2725 group of alleles]. The 24 HLA-B27 alleles (subtypes) seem to have evolved from the most widespread subtype, B*2705. Two B27 alleles have been reported to lack association with AS: B*2706 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.