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Association Study of NPPA Polymorphism with Atrial Fibrillation in a Chinese Han Population

Author: ZhanChengXiong
Tutor: RenXiang
School: Huazhong University of Science and Technology
Course: Genetics
Keywords: Atrial fibrillation NPPA Case-control association study rs5063
CLC: R541.75
Type: Master's thesis
Year: 2011
Downloads: 20
Quote: 0
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Abstract


Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice,and is increasing in both incidence and prevalence. AF can induce many cardiovascular diseases,such as heart failure and stroke, making it a major public health burden. As a complex multifactorial disorder, the incidence of AF is determined by both genetic and environmental factors. Several genes or genetic loci have been identified in monogenetic AF using linkage analysis and candidate gene resequencing. However these single-gene mutations that cause AF in families represent a minority of cases, while most of common AF cases are likely to result from multiple genes or gene-environment interaction. In recent years, three genetic loci significantly associated with AF had been identified using genome-wide association study (GWAS), and had been replicated in many different populations.In 2008, two novel moleculars, NPPA and NUP155, which are non-ionchannel determinant for AF, have extended the understanding of mechanism of AF. Since Hodgson-Zingman et al. identified the only one heterozygous frameshift mutation in NPPA in the AF family; additional studies are needed to unequivocally establish the association between NPPA and AF. We employed a case control study design to test the association between SNP rs5063 and AF, which included 384 AF patients and 844 controls without AF in a Chinese Han population. And we also screened all exons and exon–intron boundaries of NPPA by direct DNA sequence analysis in all of the AF patients. The results establish the association between a common variant rs5063 in NPPA and lone AF, and three rare variants, including p.I138T in exon 2 and c.*48G>A and c.*133G>T at the 3’-UTR of NPPA, may be potential mutations associated with lone AF. In addition, two variants at the 5’-UTR, c.-14C> T and c.-10T> C, may be polymorphisms.

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CLC: > Medicine, health > Internal Medicine > Heart, blood vessels ( circulatory ) disease > Heart disease > Arrhythmia > Atrial fibrillation and atrial flutter
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