Gene expression and genetic variation in human atria

被引:40
|
作者
Lin, Honghuang [1 ,2 ]
Dolmatova, Elena V. [9 ]
Morley, Michael P. [5 ]
Lunetta, Kathryn L. [1 ,6 ]
McManus, David D. [1 ,3 ,4 ]
Magnani, Jared W. [1 ,7 ]
Margulies, Kenneth B. [5 ]
Hakonarson, Hakon [5 ]
del Monte, Federica [11 ]
Benjamin, Emelia J. [1 ,7 ,8 ,12 ]
Cappola, Thomas P. [5 ]
Ellinor, Patrick T. [9 ,10 ,13 ,14 ]
机构
[1] Natl Heart Lung & Blood Inst & Boston Univ Framin, Framingham, MA USA
[2] Boston Univ, Sch Med, Dept Med, Sect Computat Biomed, Boston, MA 02118 USA
[3] Univ Massachusetts, Sch Med, Dept Med, Div Cardiol, Worcester, MA USA
[4] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Div Epidemiol, Worcester, MA USA
[5] Univ Penn, Sch Med, Penn Cardiovasc Inst, Philadelphia, PA 19104 USA
[6] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA
[7] Boston Univ, Sch Med, Dept Med, Sect Cardiovasc Med, Boston, MA 02118 USA
[8] Boston Univ, Sch Med, Dept Med, Sect Prevent Med, Boston, MA 02118 USA
[9] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA
[10] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA
[11] Beth Israel Deaconess Med Ctr, Cardiovasc Inst, Boston, MA 02215 USA
[12] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA
[13] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA
[14] Harvard Univ, Sch Med, Boston, MA USA
基金
美国国家卫生研究院;
关键词
Genetics; Expression quantitative trait loci; Gene expression; Atrial tissue; GENOME-WIDE ASSOCIATION; HEART-FAILURE; FIBRILLATION; DISEASE; OVEREXPRESSION; DYSFUNCTION; DISCOVERY; INTERVAL; BINDING; PROTEIN;
D O I
10.1016/j.hrthm.2013.10.051
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BACKGROUND The human left and right atria have different susceptibilities to develop atrial fibrillation (AF). However, the molecular events related to structural and functional changes that enhance AF susceptibility are still poorly understood. OBJECTIVE The purpose of this study was to characterize gene expression and genetic variation in human atria. METHODS We studied the gene expression profiles and genetic variations in 53 left atrial and 52 right atrial tissue samples collected from the Myocardial Applied Genomics Network (MAGNet) repository. The tissues were collected from heart failure patients undergoing transplantation and from unused organ donor hearts with normal ventricular function. Gene expression was profiled using the Affymetrix GeneChip Human Genome U133A Array. Genetic variation was profiled using the Affymetrix Genome-Wide Human SNP Array 6.0. RESULTS We found that 109 genes were differentially expressed between left and right atrial tissues. A total of 187 and 259 significant cis-associations between transcript levels and genetic variants were identified in left and right atrial tissues, respectively. We also found that a single nucleotide polymorphism at a known AF locus, rs3740293, was associated with the expression of MYOZ1 in both left and right atrial tissues. CONCLUSION We found a distinct transcriptional profile between the right and left atrium and extensive cis-associations between atrial transcripts and common genetic variants. Our results implicate MYOZ1 as the causative gene at the chromosome 10q22 locus for AF.
引用
收藏
页码:266 / 271
页数:6
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