title: Sex hormone receptor gene variation associated with phenotype in male hypertrophic cardiomyopathy patients.
abstract: Hypertrophic cardiomyopathy (HCM) is a clinically heterogeneous disease, which suggests that a number of factors exist which modify disease outcome. Gender may be one such factor as more males present with the disease compared with females. The aim of the present study was to determine if an association exists between genetic variation in sex hormone receptors and the development of left ventricular hypertrophy in HCM. The study population included 200 unrelated individuals from an Australian HCM cohort. Clinical evaluation was performed. Genetic analysis of the androgen receptor (AR), estrogen receptor 1 (ESR1), estrogen receptor 2 (ESR2), and aromatase (CYP19A1) genes, was carried out in all patients. Fewer (CAG)n repeats within the AR gene were significantly associated with higher maximal left ventricular wall thickness (LVWT) in males (P=0.008), adjusting for age. Male carriers of the A allele at SNP rs6915267, located in the promoter region of ESR1, had an 11% decrease in mean LVWT compared to male GG homozygotes (P=0.047). We report for the first time that variation at the AR gene is associated with left ventricular hypertrophy in males with HCM. Understanding the impact of sex hormones on phenotype will be helpful in the risk stratification and clinical management of HCM patients.
authors.affiliation: Agnes Ginges Centre for Molecular Cardiology, Centenary Institute, Sydney, Australia.
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Lind
authors.forename: Christine
authors.initials: C
authors.lastname: Chiu
authors.forename: Jodie
authors.initials: J
authors.lastname: Ingles
authors.forename: Laura
authors.initials: L
authors.lastname: Yeates
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Humphries
authors.forename: Alison K
authors.initials: AK
authors.lastname: Heather
authors.forename: Christopher
authors.initials: C
authors.lastname: Semsarian
mesh_terms: D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics*; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism
chemical_list: C410798:AR protein, human; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D012739:Gonadal Steroid Hormones; D011944:Receptors, Androgen