Analysis of TGFB1 in European and Japanese Moyamoya disease patients
Analysis of TGFB1 in European and Japanese Moyamoya disease patients
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DOI：
10.1016/j.ejmg.2012.05.002
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发表时间：
2012-10-01
影响因子：
1.9
通讯作者：
Krischek, Boris
中科院分区：
文献类型：
--
作者：
Liu, Chao;Roder, Constantin;Krischek, Boris
背景：尽管对烟雾病（MMD）的病因进行了大量的研究，但这一罕见疾病的病因仍不清楚。在以前的出版物中，我们描述了转化生长因子β 1（TGFB1）的第一外显子中的两个遗传变异，这两个变异分别相关并显示出显著性趋势。在这项研究中，我们进行了后续分析TGFB1的完整外显子1测序在欧洲和基因分型以前描述的正相关的单核苷酸多态性（SNP）在日本MMD.Methods患者：TGFB1的完整的第一外显子基因型在40例MMD患者和68名健康对照从欧洲中部。为了验证，在45名日本MMD患者和79名健康对照中进行了先前描述的SNP rs1800470和rs1800471的基因分型。分析进行毛细管测序与定制primers.Results：在欧洲队列TGFB1的第一个外显子的测序没有发现任何新的疾病相关的，也没有其他遗传变异。先前描述的rs1800471与疾病的关联性和rs1800470的显著性趋势在日本队列中无法重复。由于在欧洲MMD患者中TGFB1第一外显子的这项研究中没有发现新的遗传变异，并且由于日本MMD患者中rs1800470和rs1800471的负相关性，TGFB1的这个外显子在MMD的发生中的作用是不可能的。可能需要对更大的队列进行进一步分析，以检测导致这种疾病发生的因果遗传因素。(C)2012年Elsevier Masson SAS。All rights reserved.
Background: Despite large efforts in researching the genesis of Moyamoya disease (MMD), the etiology of this rare disease remains widely unknown. In a previous publication we described two genetic variants in the first exon of transforming growth factor beta 1 (TGFB1) which were associated and showed a tendency toward significance, respectively. In this study we performed a follow-up analysis of TGFB1 by sequencing the complete exon 1 in European and by genotyping previously described positively associated single nucleotide polymorphisms (SNPs) in Japanese patients with MMD.Methods: The complete first exon of TGFB1 was genotyped in 40 MMD patients and 68 healthy controls from central Europe. For verification, genotyping of the previously described SNPs rs1800470 and rs1800471 was performed in 45 Japanese MMD patients and 79 healthy controls. Analysis was performed by capillary sequencing with custom made primers.Results: Sequencing of the first exon of TGFB1 in the European cohort did not reveal any new disease-associated nor other genetic variations. The previously described disease association of rs1800471 and tendency toward significance of rs1800470 could not be replicated in the Japanese cohort.Conclusions: As no new genetic variants were uncovered in this study of the first exon of TGFB1 in European MMD patients and because of the negative association of rs1800470 and rs1800471 in Japanese MMD patients, a role of this exon of TGFB1 in the genesis of MMD is unlikely. Further analyses with even larger cohorts may be necessary to detect causal genetic factors that contribute to the genesis of this disease. (C) 2012 Elsevier Masson SAS. All rights reserved.