PT - JOURNAL ARTICLE AU - Corey E. Ventetuolo AU - Nandita Mitra AU - Fei Wan AU - Ani Manichaikul AU - R. Graham Barr AU - Craig Johnson AU - David A. Bluemke AU - Joao A.C. Lima AU - Hari Tandri AU - Pamela Ouyang AU - Steven M. Kawut TI - Oestradiol metabolism and androgen receptor genotypes are associated with right ventricular function AID - 10.1183/13993003.01083-2015 DP - 2016 Feb 01 TA - European Respiratory Journal PG - 553--563 VI - 47 IP - 2 4099 - http://erj.ersjournals.com/content/47/2/553.short 4100 - http://erj.ersjournals.com/content/47/2/553.full SO - Eur Respir J2016 Feb 01; 47 AB - Sex hormones are linked to right ventricular (RV) function, but the relationship between genetic variation in these pathways and RV function is unknown.We performed a cross-sectional study of 2761 genotyped adults without cardiovascular disease. The relationships between RV measures and single nucleotide polymorphisms (SNPs) in 10 candidate genes were assessed. Urinary oestradiol (E2) metabolites produced by cytochrome P4501B1 (CYP1B1) and serum testosterone were measured in women and men respectively.In African-American (AA) women, the CYP1B1 SNP rs162561 was associated with RV ejection fraction (RVEF), such that each copy of the A allele was associated with a 2.0% increase in RVEF. Haplotype analysis revealed associations with RVEF in AA (global p<7.2×10−6) and white (global p=0.05) women. In white subjects, higher E2 metabolite levels were associated with significantly higher RVEF. In men, androgen receptors SNPs (rs1337080; rs5918764) were significantly associated with all RV measures and modified the relationship between testosterone and RVEF.Genetic variation in E2 metabolism and androgen signalling was associated with RV morphology in a sex-specific manner. The CYP1B1 SNP identified is in tight linkage disequilibrium with SNPs associated with pulmonary hypertension and oncogenesis, suggesting these pathways may underpin sexual dimorphism in RV failure.Oestradiol metabolism and androgen receptor genotypes are associated with RV morphology in a sex-specific manner http://ow.ly/UbUJ3