Atrial Fibrillation Associated Chromosome 4q25 Variants Are Not Associated with PITX2c Expression in Human Adult Left Atrial Appendages

被引：44

作者：

Gore-Panter, Shamone R. ^{[1
,2
]}

Hsu, Jeffery ^{[1
,2
]}

Hanna, Peter ^{[3
]}

Gillinov, A. Marc ^{[4
]}

Pettersson, Gosta ^{[4
]}

Newton, David W. ^{[6
]}

Moravec, Christine S. ^{[5
,6
]}

Van Wagoner, David R. ^{[5
,6
]}

Chung, Mina K. ^{[5
,6
]}

Barnard, John ^{[7
]}

Smith, Jonathan D. ^{[1
,2
,5
]}

机构：

[1] Cleveland Clin, Dept Cellular & Mol Med, Cleveland, OH 44106 USA

[2] Case Western Reserve Univ, Cleveland Clin, Lerner Coll Med, Dept Mol Med, Cleveland, OH 44106 USA

[3] Case Western Reserve Univ, Cleveland Clin, Lerner Coll Med, Cleveland, OH 44106 USA

[4] Cleveland Clin, Dept Thorac & Cardiovasc Surg, Cleveland, OH 44106 USA

[5] Cleveland Clin, Dept Mol Cardiol, Cleveland, OH 44106 USA

[6] Cleveland Clin, Dept Cardiovasc Med, Cleveland, OH 44106 USA

[7] Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44106 USA

来源：

PLOS ONE | 2014年 / 9卷 / 01期

基金：

美国国家卫生研究院;

关键词：

AMINOPEPTIDASE-A; COMMON VARIANTS; SUSCEPTIBILITY; HEART; IDENTIFICATION; METAANALYSIS; ASYMMETRY; RISK; LUNG;

D O I：

10.1371/journal.pone.0086245

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Atrial Fibrillation (AF), the most common sustained arrhythmia, has a strong genetic component, but the mechanism by which common genetic variants lead to increased AF susceptibility is unknown. Genome-wide association studies (GWAS) have identified that the single nucleotide polymorphisms (SNPs) most strongly associated with AF are located on chromosome 4q25 in an intergenic region distal to the PITX2 gene. Our objective was to determine whether the AF-associated SNPs on chromosome 4q25 were associated with PITX2c expression in adult human left atrial appendages. Analysis of a lone AF GWAS identified four independent AF risk SNPs at chromosome 4q25. Human adult left atrial appendage tissue was obtained from 239 subjects of European Ancestry and used for SNP analysis of genomic DNA and determination of PITX2c RNA expression levels by quantitative PCR. Subjects were divided into three groups based on their history of AF and pre-operative rhythm. AF rhythm subjects had higher PITX2c expression than those with history of AF but in sinus rhythm. PITX2c expression was not associated with the AF risk SNPs in human adult left atrial appendages in all subjects combined or in each of the three subgroups. However, we identified seven SNPs modestly associated with PITX2c expression located in the introns of the ENPEP gene, similar to 54 kb proximal to PITX2. PITX2c expression in human adult left atrial appendages is not associated with the chromosome 4q25 AF risk SNPs; thus, the mechanism by which these SNPs are associated with AF remains enigmatic.

引用

页数：10

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