Gene expression and genetic variation in human atria
Meyers Primary Care Institute; Department of Medicine
Cardiology | Cardiovascular Diseases | Genetics and Genomics | Molecular Genetics
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
DOI of Published Version
Lin H, Dolmatova EV, Morley MP, Lunetta KL, McManus DD, Magnani JW, Margulies KB, Hakonarson H, del Monte F, Benjamin EJ, Cappola TP, Ellinor PT. Gene expression and genetic variation in human atria. Heart Rhythm. 2014 Feb;11(2):266-71. doi: 10.1016/j.hrthm.2013.10.051. Link to article on publisher's site
Heart rhythm : the official journal of the Heart Rhythm Society
Lin, Honghuang; Dolmatova, Elena V.; Morley, Michael P.; Lunetta, Kathryn L.; McManus, David D.; Magnani, Jared W.; Margulies, Kenneth B.; Hakonarson, Hakon; del Monte, Federica; Benjamin, Emelia J.; Cappola, Thomas P.; and Ellinor, Patrick T., "Gene expression and genetic variation in human atria" (2014). University of Massachusetts Medical School Faculty Publications. 344.