title: GATA2 is associated with familial early-onset coronary artery disease.
abstract: The transcription factor GATA2 plays an essential role in the establishment and maintenance of adult hematopoiesis. It is expressed in hematopoietic stem cells, as well as the cells that make up the aortic vasculature, namely aortic endothelial cells and smooth muscle cells. We have shown that GATA2 expression is predictive of location within the thoracic aorta; location is suggested to be a surrogate for disease susceptibility. The GATA2 gene maps beneath the Chromosome 3q linkage peak from our family-based sample set (GENECARD) study of early-onset coronary artery disease. Given these observations, we investigated the relationship of several known and novel polymorphisms within GATA2 to coronary artery disease. We identified five single nucleotide polymorphisms that were significantly associated with early-onset coronary artery disease in GENECARD. These results were validated by identifying significant association of two of these single nucleotide polymorphisms in an independent case-control sample set that was phenotypically similar to the GENECARD families. These observations identify GATA2 as a novel susceptibility gene for coronary artery disease and suggest that the study of this transcription factor and its downstream targets may uncover a regulatory network important for coronary artery disease inheritance.
authors.affiliation: Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, North Carolina, United States.
authors.forename: Jessica J
authors.initials: JJ
authors.lastname: Connelly
authors.forename: Tianyuan
authors.initials: T
authors.lastname: Wang
authors.forename: Julie E
authors.initials: JE
authors.lastname: Cox
authors.forename: Carol
authors.initials: C
authors.lastname: Haynes
authors.forename: Liyong
authors.initials: L
authors.lastname: Wang
authors.forename: Svati H
authors.initials: SH
authors.lastname: Shah
authors.forename: David R
authors.initials: DR
authors.lastname: Crosslin
authors.forename: A Brent
authors.initials: AB
authors.lastname: Hale
authors.forename: Sarah
authors.initials: S
authors.lastname: Nelson
authors.forename: David C
authors.initials: DC
authors.lastname: Crossman
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Granger
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Haines
authors.forename: Christopher J H
authors.initials: CJ
authors.lastname: Jones
authors.forename: Jeffery M
authors.initials: JM
authors.lastname: Vance
authors.forename: Pascal J
authors.initials: PJ
authors.lastname: Goldschmidt-Clermont
authors.forename: William E
authors.initials: WE
authors.lastname: Kraus
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Hauser
authors.forename: Simon G
authors.initials: SG
authors.lastname: Gregory
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002893:Chromosomes, Human, Pair 3; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000453:epidemiology* / Q000235:genetics*; D005091:Exons; D005190:Family; D005260:Female; D050989:GATA2 Transcription Factor / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007438:Introns; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human