title: Investigation of association between PFO complicated by cryptogenic stroke and a common variant of the cardiac transcription factor GATA4.
abstract: Patent foramen ovale (PFO) is associated with clinical conditions including cryptogenic stroke, migraine and varicose veins. Data from studies in humans and mouse suggest that PFO and the secundum form of atrial septal defect (ASDII) exist in an anatomical continuum of septal dysmorphogenesis with a common genetic basis. Mutations in multiple members of the evolutionarily conserved cardiac transcription factor network, including GATA4, cause or predispose to ASDII and PFO. Here, we assessed whether the most prevalent variant of the GATA4 gene, S377G, was significantly associated with PFO or ASD. Our analysis of world indigenous populations showed that GATA4 S377G was largely Caucasian-specific, and so subjects were restricted to those of Caucasian descent. To select for patients with larger PFO, we limited our analysis to those with cryptogenic stroke in which PFO was a subsequent finding. In an initial study of Australian subjects, we observed a weak association between GATA4 S377G and PFO/Stroke relative to Caucasian controls in whom ASD and PFO had been excluded (OR = 2.16; p = 0.02). However, in a follow up study of German Caucasians no association was found with either PFO or ASD. Analysis of combined Australian and German data confirmed the lack of a significant association. Thus, the common GATA4 variant S377G is likely to be relatively benign in terms of its participation in CHD and PFO/Stroke.
authors.affiliation: The Victor Chang Cardiac Research Institute, Darlinghurst, Australia.
authors.forename: Mahdi
authors.initials: M
authors.lastname: Moradi Marjaneh
authors.forename: Edwin P
authors.initials: EP
authors.lastname: Kirk
authors.forename: Maximilian G
authors.initials: MG
authors.lastname: Posch
authors.forename: Cemil
authors.initials: C
authors.lastname: Ozcelik
authors.forename: Felix
authors.initials: F
authors.lastname: Berger
authors.forename: Roland
authors.initials: R
authors.lastname: Hetzer
authors.forename: Robyn
authors.initials: R
authors.lastname: Otway
authors.forename: Tanya L
authors.initials: TL
authors.lastname: Butler
authors.forename: Gillian M
authors.initials: GM
authors.lastname: Blue
authors.forename: Lyn R
authors.initials: LR
authors.lastname: Griffiths
authors.forename: Diane
authors.initials: D
authors.lastname: Fatkin
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Martinson
authors.forename: David S
authors.initials: DS
authors.lastname: Winlaw
authors.forename: Michael P
authors.initials: MP
authors.lastname: Feneley
authors.forename: Richard P
authors.initials: RP
authors.lastname: Harvey
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005260:Female; D054092:Foramen Ovale, Patent / Q000150:complications* / Q000000981:diagnostic imaging / Q000235:genetics*; D050991:GATA4 Transcription Factor / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D011110:Polymorphism, Genetic; D020521:Stroke / Q000150:complications* / Q000235:genetics*; D014463:Ultrasonography; D055815:Young Adult
chemical_list: D050991:GATA4 Transcription Factor; C484170:GATA4 protein, human