A population-based study of polymorphisms in genes related to sex hormones and abdominal aortic aneurysm

• Published in: European journal of human genetics : EJHG Vol. 19; no. 3; pp. 363 - 366
• Main Authors: Golledge, Jonathan, Biros, Erik, Warrington, Nicole, Jones, Gregory T, Cooper, Matthew, van Rij, Andre M, Palmer, Lyle J, Norman, Paul E
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.03.2011; Nature Publishing Group
• Subjects: 631/208/457/649; 631/45/776; 692/699/75/593; 692/700/478/2772; Abdomen; Aged; Aged, 80 and over; Androgens; Aneurysm; Aneurysms; Aorta; Aortic Aneurysm, Abdominal - genetics; Bioinformatics; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Blood and lymphatic vessels; Cardiology. Vascular system; Cardiovascular disease; Cohort Studies; Cytochrome; Cytochrome P450; Cytogenetics; Databases, Genetic; Diseases of the aorta; Enzymes; Estrogens; Fundamental and applied biological sciences. Psychology; Gene Expression; General aspects. Genetic counseling; Genes; Genetic Predisposition to Disease; Genetics; Genetics of eukaryotes. Biological and molecular evolution; Genetics, Population; Genotype; Gonadal Steroid Hormones - analysis; Haplotypes; Hormones; Human Genetics; Humans; Male; Medical genetics; Medical sciences; Metabolism; Molecular and cellular biology; New Zealand; Polymorphism, Single Nucleotide; Polypeptides; Population; Population studies; Reductase; Risk Factors; Scholarships & fellowships; Sex; Sex hormones; Short Report; Single-nucleotide polymorphism; Software packages; Surgery; Ultrasonic imaging; New Zealand; Queensland Australia; Australia; Western Australia Australia; sex hormones; aneurysm; aorta; Human; Hormone; Sex; Cardiovascular disease; Aortic aneurysm; Abdominal aorta; Vascular disease; Gene; Genetics; Population; Polymorphism
• ISSN: 1018-4813; 1476-5438; 1476-5438
• DOI: 10.1038/ejhg.2010.182

Male gender and family history are risk factors for abdominal aortic aneurysm (AAA). We hypothesized that genes involved in sex hormones might be important in AAA. We investigated the association of aortic diameter with single-nucleotide polymorphisms (SNPs) in genes determining circulating sex hormones and their action. We genotyped 74 tagging SNPs across four genes ( steroid 5α reductase, subfamily A, polypeptide 1 (SRD5A1) , cytochrome P450, family 19, subfamily A, polypeptide 1 (CYP19A1) , androgen receptor (AR) and estrogen receptor 2 (ESR2) ) related to sex hormone production and action in 1711 men, 640 of whom had an AAA. One genotype was also assessed in an independent cohort of 782 men, of whom 513 had large AAAs. Associations were assessed adjusting for other risk factors for AAA. One SNP in CYP19A1 was strongly associated with aortic diameter. Subjects who had the rare homozygote genotype ( TT ) for CYP19A1g.49412370C>T (SNP ID rs1961177), had an increased aortic diameter (coefficient 5.058, SE 1.394, P =0.0003, under a recessive model). This SNP was not associated with aortic diameter in an independent cohort, which included patients with larger AAAs. Our findings do not support an important role of genetic polymorphisms in genes determining sex hormones in aortic dilatation in men. The association of one SNP in CYPA9A1 with small but not large AAA may suggest differences between AAA formation and progression. This SNP warrants further investigation in another large population, including patients with small AAAs.