title: Evidence from single nucleotide polymorphism analyses of ADVANCE study demonstrates EFNB3 as a hypertension risk gene.
abstract: EPH kinases and their ligands, ephrins (EFNs), have vital and diverse biological functions. We recently reported that Efnb3 gene deletion results in hypertension in female but not male mice. These data suggest that EFNB3 regulates blood pressure in a sex- and sex hormone-dependent way. In the present study, we conducted a human genetic study to assess the association of EFNB3 single nucleotide polymorphisms with human hypertension risks, using 3,448 patients with type 2 diabetes from the ADVANCE study (Action in Diabetes and Vascular Disease: Peterax and Diamicron MR Controlled Evaluation). We have observed significant association between 2 SNPs in the 3' untranslated region or within the adjacent region just 3' of the EFNB3 gene with hypertension, corroborating our findings from the mouse model. Thus, our investigation has shown that EFNB3 is a hypertension risk gene in certain individuals.
authors.affiliation: Research Centre, Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec H2X 0A9, Canada.
authors.forename: Johanne
authors.initials: J
authors.lastname: Tremblay
authors.affiliation: Research Centre, Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec H2X 0A9, Canada.
authors.forename: Yujia
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Research Centre, Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec H2X 0A9, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Raelson
authors.affiliation: Research Centre, Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec H2X 0A9, Canada.
authors.forename: Francois-Christophe
authors.initials: FC
authors.lastname: Marois-Blanchet
authors.affiliation: Research Centre, Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec H2X 0A9, Canada.
authors.forename: Zenghui
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Research Centre, Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec H2X 0A9, Canada.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Luo
authors.affiliation: Research Centre, Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec H2X 0A9, Canada.
authors.forename: Edward
authors.initials: E
authors.lastname: Bradley
authors.affiliation: The George Institute for Global Health, University of Sydney Sydney, New South Wales, 2006, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Chalmers
authors.affiliation: The George Institute for Global Health, University of Sydney Sydney, New South Wales, 2006, Australia.|The George Institute for Global Health, University of Oxford, Oxford, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Woodward
authors.affiliation: Department of Epidemiology, Johns Hopkins University, Baltimore MD, USA.|Department of Physiology, University of Melbourne, Victoria 3010, Australia.
authors.forename: Stephen
authors.initials: S
authors.lastname: Harrap
authors.affiliation: Research Centre, Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec H2X 0A9, Canada.
authors.forename: Pavel
authors.initials: P
authors.lastname: Hamet
authors.affiliation: Research Centre, Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, Quebec H2X 0A9, Canada.
authors.forename: Jiangping
authors.initials: J
authors.lastname: Wu
mesh_terms: D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D036389:Ephrin-B3 / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000209:etiology / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: D036389:Ephrin-B3