Common genetic polymorphisms in Moyamoya and atherosclerotic disease in Europeans
Common genetic polymorphisms in Moyamoya and atherosclerotic disease in Europeans
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DOI：
10.1007/s00381-010-1241-8
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发表时间：
2011-02-01
影响因子：
1.4
通讯作者：
Krischek, Boris
中科院分区：
文献类型：
--
作者：
Roder, Constantin;Peters, Vera;Krischek, Boris
烟雾病是日本儿童中最常见的脑血管疾病。该疾病的病因仍然广泛未知。一些出版物描述了受影响血管壁的组织病理学变化，类似于动脉粥样硬化中所见的变化。在这项研究中，我们分析了欧洲烟雾病患者的 DNA 中与动脉粥样硬化变化相关的单核苷酸多态性。我们对 11 个基因（ELN、LIMK1、CDKN2A/B、CXCL12、Pseudogene ENSG00000197218、PSRC1、MTHFD1L、SMAD3、MIA3、 PDGF-B、TIMP2）将烟雾病患者的 40 个 DNA 样本与来自中欧的 68 个健康对照进行比较。烟雾病 (MMD) 相关症状的平均发病年龄为 15.4 岁。通过使用定制引物对包含遗传区域的 SNP 进行测序来进行基因分型。我们发现一个 SNP (rs599839 [A/G]，OR = 2.17，95% CI = 1.17, 4.05；p = 0.01) 与位于 PSRC-1 基因 3' UTR 区域的风险等位基因 G 存在很强的关联性。 ELN 和 CXCL12 基因中或附近的另外 3 个 SNP（rs8326、rs34208922、rs501120）显示出 p 值在 0.1 至 0.2 之间的风险等位基因的倾向，但在我们的队列中并未达到统计显着性。我们的结果表明烟雾病和动脉粥样硬化疾病的发病过程可能存在相似的共同过程。在更大的欧洲队列中进行的进一步分析以及在不同种族患者中的复制可能会导致早期发现有MMD风险的患者，并随后进行未来的病因治疗。
Moyamoya is the most common cerebrovascular disease in children in Japan. The disease's etiology is still widely unknown. Several publications describe histopathological changes in the walls of affected vessels similar to those seen in atherosclerosis. In this study, we analyzed the DNA of European patients with Moyamoya disease for single nucleotide polymorphisms associated with atherosclerotic changes.We genotyped 17 SNPs in or adjacent to 11 genes (ELN, LIMK1, CDKN2A/B, CXCL12, Pseudogene ENSG00000197218, PSRC1, MTHFD1L, SMAD3, MIA3, PDGF-B, TIMP2) comparing 40 DNA samples of Moyamoya disease patients to 68 healthy controls from central Europe. The mean age of onset of Moyamoya disease (MMD)-related symptoms was 15.4 years of age. Genotyping was performed by sequencing the SNP containing genetic regions with custom-made primers.We found strong association of one SNP (rs599839 [A/G], OR = 2.17, 95% CI = 1.17, 4.05; p = 0.01) with the risk allele G located in the 3' UTR region of the PSRC-1 gene. Three further SNPs (rs8326, rs34208922, rs501120) in or adjacent to the genes ELN and CXCL12 showed tendencies towards risk alleles with p values between 0.1 and 0.2 but did not reach statistical significance in our cohort.Our results indicate a possible parallel of common processes in the genesis of Moyamoya disease and atherosclerotic disease. Further analyses in larger European cohorts and replication in patients of different ethnicity may lead to possible early detection of patients at risk for developing MMD and subsequently to future causative therapies.