Genetic mapping of ossification of the posterior longitudinal ligament of the spine
Genetic mapping of ossification of the posterior longitudinal ligament of the spine
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DOI：
10.1086/301868
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发表时间：
1998-06-01
影响因子：
9.8
通讯作者：
Leppert, M
中科院分区：
文献类型：
--
作者：
Koga, H;Sakou, T;Leppert, M
脊椎后纵韧带骨化(OPLL)是日本人和整个亚洲人的一种常见疾病。对其流行率的估计在1.9%-4.3%之间。尽管其病因被认为涉及多种因素，但流行病学和家族学研究强烈表明，遗传易感性与OPLL的发病机制有关。在这项研究中，我们报告了OPLL的易感基因，位于染色体6p上，靠近人类白细胞抗原复合体。这一定位的证据来自对来自53个日本家庭的91对受影响的同胞的遗传连锁研究。在这项同胞配对研究中，D6S276，一个靠近人类白细胞抗原复合体的标记，提供了与OPLL基因座有很强的显著连锁(P=0.000006)的证据。该区域的一个候选基因，即11A2胶原蛋白，被分析了在受影响的先证者中是否存在分子变异。在发现的19个不同的变异中，有4个与OPLL有很强的统计学相关性(最高P=.0004)。这些连锁和关联的观察结果表明，OPLL的一个遗传位点位于染色体6p上的HLA区附近。
Ossification of the posterior longitudinal ligament of the spine (OPLL) is recognized as a common disorder among Japanese and throughout Asia. Estimates of its prevalence are in the range of 1.9%-4.3%. Although its etiology is thought to involve a multiplicity of factors, epidemiological and family studies strongly implicate genetic susceptibility in the pathogenesis of OPLL. In this study we report an identification of a predisposing locus for OPLL, on chromosome 6p, close to the HLA complex. The evidence for this localization is provide by a genetic-linkage study of 91 affected sib pairs from 53 Japanese families. In this sib-pair study, D6S276, a marker lying close to the HLA complex, gives evidence for strongly significant linkage (P =.000006) to the OPLL locus. A candidate gene in the region, that for collagen 11A2, was analyzed for the presence of molecular variants in affected probands. Of 19 distinct variants identified, 4 showed strong statistical associations with OPLL (highest P =.0004). These observations of linkage and association, taken together, show that a genetic locus for OPLL lies close to the HLA region, on chromosome 6p.