Association study of COL9A2 with lumbar disc disease in the Japanese population
Association study of COL9A2 with lumbar disc disease in the Japanese population
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DOI：
10.1007/s10038-006-0062-9
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发表时间：
2006-01-01
影响因子：
3.5
通讯作者：
Ikegawa, Shiro
中科院分区：
文献类型：
--
作者：
Seki, Shoji;Kawaguchi, Yoshiharu;Ikegawa, Shiro
腰椎间盘病（LDD）是一种常见的肌肉骨骼疾病，具有很强的遗传决定因素。据报道，在芬兰人群中，编码IX型胶原蛋白12（IX）链的COL 9A 2中引起氨基酸取代（Trp 2等位基因）的单核苷酸多态性（SNP）与LDD相关。然而，在不同人群中的复制研究产生了有争议的结果。为了进一步研究日本人COL 9A 2与LDD的相关性，我们检测了470名LDD患者（平均年龄35岁）沿着658名对照（平均年龄48岁）中COL 9A 2（包括Trp 2）的SNP。我们在COL 9A 2中总共鉴定了43个序列变异。选择包括Trp 2在内的9个SNP并进行基因分型。在Bonferroni校正后，这些SNP均未显示出关联。与芬兰人群中的观察结果不同，Trp 2在日本人中很常见，与LDD没有明显的关联。然而，我们确实观察到COL 9A 2特异性单倍型与LDD相关（P=0.025;排列检验）;这种相关性在严重腰椎间盘退变患者中更为显著（P=0.011）。因此，Trp 2与LDD的关联没有被复制，但在日本LDD中可能存在Trp 2以外的COL 9A 2易感等位基因。
Lumbar disc disease (LDD) is a common musculo-skeletal disease with strong genetic determinants. In a Finnish population, a single nucleotide polymorphism (SNP) causing an amino-acid substitution (Trp2 allele) in COL9A2, which encodes the 12 (IX) chain of type IX collagen, has been reported to associate with LDD. However, replication studies in different populations have produced controversial results. To further investigate the association of COL9A2 with LDD in Japanese, we examined SNPs in COL9A2, including Trp2, in 470 LDD patients (mean age 35) along with 658 controls (mean age 48). We identified a total of 43 sequence variations in COL9A2. Nine SNPs, including Trp2, were selected and genotyped. After Bonferroni's correction, none of these SNPs showed association. Unlike observations in the Finnish population, Trp2 was common in Japanese, and no association with LDD was apparent. However, we did see association of a COL9A2 specific haplotype with LDD (P=0.025; permutation test); this association is more significant in patients with severe lumbar disc degeneration (P=0.011). Thus, the association of Trp2 with LDD was not replicated, but COL9A2 susceptibility allele(s) other than Trp2 may be present in Japanese LDD.