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Several genes have been associated with the presence of <jats:styled-content style=\"fixed-case\">BAV<\/jats:styled-content>, notably some members of the <jats:styled-content style=\"fixed-case\">GATA<\/jats:styled-content> family of transcription factors that play important roles in cardiac embryogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A case\u2010control study with 122 unrelated and ethnically matched patients with bicuspid and 154 with tricuspid aortic valve was performed. All exons of <jats:italic><jats:styled-content style=\"fixed-case\">GATA<\/jats:styled-content>4<\/jats:italic>,<jats:italic> <jats:styled-content style=\"fixed-case\">GATA<\/jats:styled-content>5,<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">GATA<\/jats:styled-content>6<\/jats:italic> genes were sequenced searching for variants. Frequencies were compared and functional effects of rare variants were analysed by informatic prediction tools.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Four rare and potentially pathogenic variants were identified in only five sporadic cases: a missense p.Arg202Gln (rs782614097) in <jats:italic><jats:styled-content style=\"fixed-case\">GATA<\/jats:styled-content>5<\/jats:italic> and three synonymous variants, p.Cys274= (rs55980825) and p.His302= (rs201516339) in <jats:italic><jats:styled-content style=\"fixed-case\">GATA<\/jats:styled-content>4<\/jats:italic>, and p.Asn458= (rs143026087) in <jats:italic><jats:styled-content style=\"fixed-case\">GATA<\/jats:styled-content>6<\/jats:italic>. Minor alleles of p.His302=, p.Arg202Gln and rs3764962 are enriched in <jats:styled-content style=\"fixed-case\">BAV<\/jats:styled-content> patients compared to Ex<jats:styled-content style=\"fixed-case\">AC<\/jats:styled-content> database (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.01, 0.03, and 0.01 respectively). In addition, a common polymorphism in <jats:italic><jats:styled-content style=\"fixed-case\">GATA<\/jats:styled-content>5<\/jats:italic> (p.Asp203=, rs41305803) is associated with <jats:styled-content style=\"fixed-case\">BAV<\/jats:styled-content> showing a protective effect in carriers of the minor allele (<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content> [95%<jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>]\u00a0=\u00a00.45[0.25\u20100.81]; <jats:italic>P<\/jats:italic>\u00a0=\u00a00.004).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study associates additional genetic variants in <jats:italic><jats:styled-content style=\"fixed-case\">GATA<\/jats:styled-content>4<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">GATA<\/jats:styled-content>5<\/jats:italic> with <jats:styled-content style=\"fixed-case\">BAV<\/jats:styled-content>, supporting the implication of these genes in the development of this valvulopathy. The discovery of all the genetic factors involved will contribute to a better understanding of the process and, therefore, to detect a genetic predisposition and even to the identification of therapeutic targets.<\/jats:p><\/jats:sec>","DOI":"10.1111\/eci.13027","type":"journal-article","created":{"date-parts":[[2018,9,19]],"date-time":"2018-09-19T12:01:38Z","timestamp":1537358498000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Variants in cardiac <scp>GATA<\/scp> genes associated with bicuspid aortic valve"],"prefix":"10.1111","volume":"48","author":[{"given":"Cristina","family":"Alonso\u2010Montes","sequence":"first","affiliation":[{"name":"Bone and Mineral Research Unit REDinREN\u2010ISCIII Hospital Universitario Central de Asturias Universidad de Oviedo Oviedo Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria del Principado de Asturias (ISPA) Oviedo 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