A large-scale genetic association study of ossification of the posterior longitudinal ligament of the spine
A large-scale genetic association study of ossification of the posterior longitudinal ligament of the spine
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DOI：
10.1007/s00439-006-0170-9
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发表时间：
2006-07-01
期刊：
影响因子：
5.3
通讯作者：
Ikegawa, Shiro
中科院分区：
文献类型：
--
作者：
Horikoshi, Taizo;Maeda, Koichi;Ikegawa, Shiro
迄今为止的研究已经确定了几个与脊柱后纵韧带骨化（OPLL）病因学有关的基因;然而，它们的发病相关性仍然不清楚。本研究的目的是通过一项大规模的病例对照关联研究来确定OPLL的易感基因，并重新研究以前报道的关联。对711例散发性OPLL患者和896例对照者的35个候选基因共109个单核苷酸多态性（SNP）进行基因分型。患者和对照组之间等位基因和基因型分布的差异使用卡方检验和Bonferroni校正进行评估。我们还根据性别、年龄和骨化椎骨的数量将患者分成亚组，分析了相关性。三个基因中的五个SNP的标称P值低于0.05。TGF 3基因的内含子SNP（P=0.00040）显示出最显著的关联。先前报道的COL 11 A2、NPPS和TGFB 1与OPLL的相关性无法重现。此外，在基于性别、年龄或骨化椎骨数量的分层分析中未检测到显著相关性。TGFB 3值得进一步研究，因为它位于与OPLL正相关的基因组区域内。
Research to date has identified several genes that are implicated in the etiology of ossification of the posterior longitudinal ligament of the spine (OPLL); however, their pathogenetic relevance remains obscure. The aim of this study is to identify susceptibility genes for OPLL through a large-scale case-control association study and to re-examine previously reported associations. A total of 109 single nucleotide polymorphisms (SNPs) in 35 candidate genes were genotyped for 711 sporadic OPLL patients and 896 controls. The differences in allelic and genotypic distribution between patients and controls were assessed using the chi(2) test with Bonferroni's correction. We also analyzed the association by separating patients into subgroups according to sex, age and the number of ossified vertebrae. The nominal P values fell below 0.05 for five SNPs in three genes. An intronic SNP in the TGF3 gene (P=0.00040) showed the most significant association. Previously reported associations of COL11A2, NPPS and TGFB1 with OPLL could not be reproduced. Further, no significant associations were detected in stratified analyses based on sex, age or the number of ossified vertebrae. TGFB3 warrants further investigation because it is located within a genomic region that has been positively linked with OPLL.