Identification of NPPA variants associated with atrial fibrillation in a Chinese GeneID population
Identification of NPPA variants associated with atrial fibrillation in a Chinese GeneID population
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中国 GeneID 人群中与心房颤动相关的 NPPA 变异的鉴定
DOI：
10.1016/j.cca.2009.12.019
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发表时间：
2010-04-02
影响因子：
5
通讯作者：
Wang, Qing Kenneth
中科院分区：
文献类型：
--
作者：
Ren, Xiang;Xu, Chengqi;Wang, Qing Kenneth
背景：在1个心房颤动(房颤)家系中发现了NPPA基因移码突变，但要明确NPPA与房颤的遗传关联还有待进一步研究。方法：对384例散发性房颤患者和844例正常对照进行病例对照关联研究和突变分析。采用高分辨熔融分析进行基因分型。结果：单核苷酸多态rs5063与孤立性房颤存在显著的等位基因关联(p=0.015，OR=1.63；校正后p=0.003)。在加性或显性模型的假设下，基因型关联显著(调整后的p分别为0.005和0.007)。在NPPA中发现了6个新的变异体，其中2个在5‘-非编码区，2个在3’-非编码区，2个错义替换。844名对照人群中未发现c.413T>；C、c.*48G>；A和c.*133G>；T等位基因变异，其余均在对照人群中发现。因此，除了在家族性房颤病例中发现突变的致病基因外，NPPA还是孤立性房颤的易感基因。(C)2010爱思唯尔B.V.保留所有权利。
Background: A frameshift mutation in the NPPA gene was identified in 1 family with atrial fibrillation (AF), however, further studies are needed to establish unequivocally the genetic association between NPPA and AF.Methods: A case control association study and mutational analysis of NPPA were performed with 384 sporadic AF patients and 844 controls from a Chinese GeneID population. Genotyping was performed using High-Resolution Melt analysis. Mutational analysis was performed using direct DNA sequencing analysis.Results: Significant allelic association was detected between single nucleotide polymorphism (SNP) rs5063 and lone AF (p=0.015, OR=1.63; adjusted p=0.003). Genotypic association was significant assuming an additive or dominant model (adjusted p=0.005 and 0.007, respectively). Six new variants were identified in NPPA, including 2 in the 5'-UTR, 2 in the 3'-UTR, and 2 missense substitutions. Variants c.413T>C, c.*48G>A and c.*133G>T were not present in 844 controls, and the others were identified in controls.Conclusions: Variants in NPPA confer risk of lone AF in a Chinese population. Thus, in addition to being a disease-causing gene with mutations identified in familial AF cases, NPPA is a susceptibility gene for lone AF. (C) 2010 Elsevier B.V. All rights reserved.