Association of the MSX2 gene polymorphisms with ankylosing spondylitis in Japanese
Association of the MSX2 gene polymorphisms with ankylosing spondylitis in Japanese
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DOI：
10.1007/s10038-008-0265-3
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发表时间：
2008-05-01
影响因子：
3.5
通讯作者：
Ikegawa, Shiro
中科院分区：
文献类型：
--
作者：
Furuichi, Tatsuya;Maeda, Koichi;Ikegawa, Shiro
强直性脊柱炎（AS）的病因学中涉及到几个基因，然而，这些基因的意义，除了HLA-B27仍有待阐明。在这项研究中，我们研究了AS与新的候选基因和以前报道的基因以外的HLA-B27。我们通过序贯筛选共检测了15个基因的45个单核苷酸多态性（SNP）。我们首先对170名日本AS患者和896名对照进行SNP基因分型（第一次筛选）。然后，我们在第一次筛选中对另外108名日本患者（第二次筛选）的8个SNP进行基因分型，P < 0.05。我们通过对219名台湾AS患者和185名对照者进行基因分型，检查了最显著SNP相关性的复制。当第一和第二筛选组合时，四个SNP显示P < 0.05的名义显著性。新的候选基因MSX 2的内含子SNP（IVS 1 + 996 G> A）显示出最显著的关联（P = 0.0030）。这种关联在我们的台湾人群中没有重复，但是，在SNP的等位基因频率分布中，与日本人群有相同的趋势。在先前报道的与AS相关的基因中，只有一个同义SNP，即ANKH中的c.963T > G，在日本人群中显示出边缘相关性（P = 0.045）。
Several genes have been implicated in the etiology of ankylosing spondylitis (AS); however, the significance of these genes except HLA-B27 remains to be elucidated. In this study, we examined the association of AS with novel candidate genes and previously reported genes other than HLA-B27. We examined a total of 45 single nucleotide polymorphisms (SNPs) in 15 genes by a sequential screening. We first genotyped 170 Japanese AS patients and 896 controls for the SNPs (first screen). Then, we genotyped eight SNPs with P < 0.05 in the first screen for 108 additional Japanese patients (second screen). We checked the replication of the association of the most significant SNP by genotyping 219 Taiwanese AS patients and 185 controls. When the first and second screens were combined, four SNPs showed nominal significance of P < 0.05. An intronic SNP (IVS1 + 996G > A) in MSX2, a novel candidate gene, showed the most significant association (P = 0.0030). The association was not replicated in our Taiwanese population; however, there was the same trend with the Japanese population in the allelic frequency distribution of the SNP. In the genes previously reported to have association with AS, only one synonymous SNP, c.963T > G in ANKH, showed a marginal association in the Japanese population (P = 0.045).