TY - JOUR
T1 - Genetic variation in sex hormone genes influences heel ultrasound parameters in middle-aged and elderly men: Results from the European Male Aging Study (EMAS)
AU - Limer, Kate L.
AU - Thomson, Wendy
AU - Boonen, Steven
AU - Borghs, Herman
AU - Vanderschueren, Dirk
AU - Adams, Judith E.
AU - Ward, Kate A.
AU - Platt, Hazel
AU - Payne, Debbie
AU - John, Sally L.
AU - Bartfai, Gyorgy
AU - Casanueva, Felipe
AU - Forti, Gianni
AU - Giwercman, Aleksander
AU - Han, Thang S.
AU - Kula, Krzysztof
AU - Lean, Michael E.
AU - Pendleton, Neil
AU - Punab, Margus
AU - Wu, Frederick
AU - Petrone, Luisa
AU - Cilotti, Antonio
AU - Slowikowska-Hilczer, Jolanta
AU - Walczak-Jedrzejowska, Renata
AU - Huhtaniemi, Ilpo
AU - Silman, Alan
AU - O'Neill, Terence
AU - Finn, Joseph
AU - Steer, Philip
AU - Tajar, Abdelouahid
AU - Lee, David
AU - Pye, Stephen
AU - Ocampo, Marta
AU - Lage, Mary
AU - Földesi, Imre
AU - Fejes, Imre
AU - Korrovitz, Paul
AU - Jiang, Min
PY - 2009/2
Y1 - 2009/2
N2 - 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 40-79 yr of age were recruited from population registers in eight European centers for the European Male Aging 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 BMD. The relationships between QUS parameters and polymorphisms were assessed using linear regression adjusting for age and center. A total of 2693 men, with a mean age of 60.1 ± 11.1 (SD) yr were included in the analysis. Their mean 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 a linkage disequilibrium (LD) block within CYP19A1, peaking at the TCT indel with the deletion allele associating with reduced ultrasound BMD in heterozygotes (β =-0.016, ρ = -0.005) and homozygotes (β = -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. © 2009 American Society for Bone and Mineral Research.
AB - 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 40-79 yr of age were recruited from population registers in eight European centers for the European Male Aging 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 BMD. The relationships between QUS parameters and polymorphisms were assessed using linear regression adjusting for age and center. A total of 2693 men, with a mean age of 60.1 ± 11.1 (SD) yr were included in the analysis. Their mean 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 a linkage disequilibrium (LD) block within CYP19A1, peaking at the TCT indel with the deletion allele associating with reduced ultrasound BMD in heterozygotes (β =-0.016, ρ = -0.005) and homozygotes (β = -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. © 2009 American Society for Bone and Mineral Research.
KW - Aging
KW - CYP19A1
KW - Genetics
KW - Quantitative heel ultrasound
KW - Sex hormones
U2 - 10.1359/jbmr.080912
DO - 10.1359/jbmr.080912
M3 - Article
C2 - 18767927
SN - 0884-0431
VL - 24
SP - 314
EP - 323
JO - Journal of Bone and Mineral Research
JF - Journal of Bone and Mineral Research
IS - 2
ER -