TY - JOUR
T1 - Genetic variations in sex steroid-related genes as predictors of serum estrogen levels in men
AU - Eriksson, Anna L.
AU - Lorentzon, Mattias
AU - Vandenput, Liesbeth
AU - Labrie, Fernand
AU - Lindersson, Marie
AU - Syvänen, Ann Christine
AU - Orwoll, Eric S.
AU - Cummings, Steven R.
AU - Zmuda, Joseph M.
AU - Ljunggren, Östen
AU - Karlsson, Magnus K.
AU - Mellström, Dan
AU - Ohlsson, Claes
N1 - Funding Information:
This work was supported by the Swedish Research Council, the Swedish Foundation for Strategic Research, the Avtal om Läkarutbildning och Forskning/Läkarutbildningsavtalet research grant in Gothenburg, the Lundberg Foundation, the Torsten and Ragnar Söderberg's Foundation, the Novo Nordisk Foundation, and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) Grant R01-AR051124. The SNP Technology Platform in Uppsala was established by funding from the Knut and Alice Wallenberg Foundation via Wallenberg Consortium North (WCN). The Osteoporotic Fractures in Men (MrOS) US Study is supported by National Institutes of Health funding. The following institutes provided support: NIAMS, the National Institute on Aging (NIA), the National Center for Research Resources (NCRR), and NIH Roadmap for Medical Research under the following grant numbers: U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01-AG027810, and UL1 RR024140.
PY - 2009/3
Y1 - 2009/3
N2 - Context: The risk of many conditions, including prostate cancer, breast cancer, and osteoporosis, is associated with serum levels of sex steroids.Objective: The aim of the study was to identify genetic variations in sex steroid-related genes that are associated with serum levels of estradiol (E2) and/or testosterone in men.Design: Genotyping of 604 single nucleotide polymorphisms in 50 sex steroid-related candidate genes was performed in the Gothenburg Osteoporosis and Obesity Determinants (GOOD) study (n = 1041 men; age, 18.9 ± 0.6 yr). Replications of significant associations were performed inthe Osteoporotic Fractures in Men (MrOS) Sweden study (n = 2568 men; age, 75.5 ± 3.2 yr) and in the MrOS US study (n = 1922 men; age, 73.5 ± 5.8 yr). Serum E2, testosterone, and estrone (E1) levels were analyzed using gas chromatography/mass spectrometry.Results: The screening in the GOOD cohort identified the single nucleotide polymorphism rs2470152 in intron 1 of the CYP19 gene, which codes for aromatase, responsible for the final step of the biosynthesis of E2 and E1,to be most significantly associated with serum E2 levels (P = 2 × 10-6). This association was confirmed both in the MrOS Sweden study (P = 9 × 10-7) and in the MrOS US study (P= 1 × 10-4). When analyzed in all subjects (n = 5531), rs2470152 was clearly associated with both E2(P = 2 × 10-14) and E1 (P = 8 × 10-19) levels. In addition, this polymorphism was modestly associated with lumbar spine BMD (P < 0.01) and prevalent self-reported fractures (P < 0.05). Conclusions: rs2470152 of the CYP19 gene is clearly associated with serum E2 and E1 levels in men.
AB - Context: The risk of many conditions, including prostate cancer, breast cancer, and osteoporosis, is associated with serum levels of sex steroids.Objective: The aim of the study was to identify genetic variations in sex steroid-related genes that are associated with serum levels of estradiol (E2) and/or testosterone in men.Design: Genotyping of 604 single nucleotide polymorphisms in 50 sex steroid-related candidate genes was performed in the Gothenburg Osteoporosis and Obesity Determinants (GOOD) study (n = 1041 men; age, 18.9 ± 0.6 yr). Replications of significant associations were performed inthe Osteoporotic Fractures in Men (MrOS) Sweden study (n = 2568 men; age, 75.5 ± 3.2 yr) and in the MrOS US study (n = 1922 men; age, 73.5 ± 5.8 yr). Serum E2, testosterone, and estrone (E1) levels were analyzed using gas chromatography/mass spectrometry.Results: The screening in the GOOD cohort identified the single nucleotide polymorphism rs2470152 in intron 1 of the CYP19 gene, which codes for aromatase, responsible for the final step of the biosynthesis of E2 and E1,to be most significantly associated with serum E2 levels (P = 2 × 10-6). This association was confirmed both in the MrOS Sweden study (P = 9 × 10-7) and in the MrOS US study (P= 1 × 10-4). When analyzed in all subjects (n = 5531), rs2470152 was clearly associated with both E2(P = 2 × 10-14) and E1 (P = 8 × 10-19) levels. In addition, this polymorphism was modestly associated with lumbar spine BMD (P < 0.01) and prevalent self-reported fractures (P < 0.05). Conclusions: rs2470152 of the CYP19 gene is clearly associated with serum E2 and E1 levels in men.
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U2 - 10.1210/jc.2008-1283
DO - 10.1210/jc.2008-1283
M3 - Article
C2 - 19116238
AN - SCOPUS:62349126794
SN - 0021-972X
VL - 94
SP - 1033
EP - 1041
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 3
ER -