Genetic Variation in Sex Hormone Genes Influences Heel Ultrasound Parameters in Middle Aged and Elderly Men: Results From the European Male Ageing Study (EMAS)

Abstract Genes involved in sex hormone pathways are candidates for influencing bone strength. Polymorphisms in these genes were tested for association with heel quantitative ultrasound (QUS) parameters in middle aged and elderly European Men. Men aged 40-79 years were recruited from population registers in 8 European centres for the European Male Ageing Study (EMAS). Polymorphisms were genotyped in AR, ESR1, ESR2, CYP19A1, CYP17A1, SHBG, SRD5A2, LHB and LHCGR. QUS parameters broadband ultrasound attenuation (BUA) and speed of sound (SOS) were measured in the heel and used to derive bone mineral density (BMD). The relationships between QUS parameters and polymorphisms were assessed using linear regression adjusting for age and centre. 2693 men, mean+/-SD age 60.1+/-11.1 years were included in the analysis. Their mean+/-SD BUA was 80.0+/-18.9 dB/Mhz, SOS was 1550.2+/-34.1 m/s and BMD was 0.542+/-0.141 g/cm(2). Significant associations were observed between multiple SNPs in an LD block within CYP19A1, peaking at the TCT indel with the deletion allele associating with reduced ultrasound BMD in heterozygotes (beta=-0.016, p=-0.005) and homozgotes (beta=-0.029, p=0.001). The results for BUA and SOS were similar. Significant associations with QUS parameters were also observed for the CAG repeat in AR and SNPs in CYP17A1, LHCGR and ESR1. Our data confirm evidence of association between bone QUS parameters and polymorphisms in CYP19A1 as well as modest associations with polymorphisms in CYP17A1, ESR1, LHCGR and AR in a population sample of European men; this supports a role for genetically-determined sex hormone actions in influencing male bone health.

Jaar van publicatie:2009

BOF-keylabel:ja

IOF-keylabel:ja

BOF-publication weight:6

CSS-citation score:1

Auteurs:International

Authors from:Higher Education