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Genetic Variations in Sex Steroid-Related Genes as Predictors of Serum Estrogen Levels in Men

Eriksson, Anna L.; Lorentzon, Mattias; Vandenput, Liesbeth; Labrie, Fernand; Lindersson, Marie; Syvanen, Ann-Christine; Orwoll, Eric S.; Cummings, Steven R.; Zmuda, Joseph M. and Ljunggren, Osten, et al. (2009) In Journal of Clinical Endocrinology and Metabolism 94(3). p.1033-1041
Abstract
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 in the 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... (More)
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 in the 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 x 10(-6)). This association was confirmed both in the MrOS Sweden study (P = 9 x 10(-7)) and in the MrOS US study (P = 1 x 10(-4)). When analyzed in all subjects (n = 5531), rs2470152 was clearly associated with both E2 (P = 2 x 10(-14)) and E1 (P = 8 x 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. (J Clin Endocrinol Metab 94: 1033-1041, 2009) (Less)
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Journal of Clinical Endocrinology and Metabolism
volume
94
issue
3
pages
1033 - 1041
publisher
The Endocrine Society
external identifiers
  • wos:000264020700048
  • scopus:62349126794
  • wos:000259411001447
  • pmid:19116238
ISSN
1945-7197
DOI
10.1210/jc.2008-1283
language
English
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yes
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96b88cdc-ae15-4961-9fef-01377ce959ca (old id 1404815)
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http://www.ncbi.nlm.nih.gov/pubmed/19116238?dopt=Abstract
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2009-02-03 10:10:17
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2017-10-01 04:30:29
@article{96b88cdc-ae15-4961-9fef-01377ce959ca,
  abstract     = {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 in the 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 x 10(-6)). This association was confirmed both in the MrOS Sweden study (P = 9 x 10(-7)) and in the MrOS US study (P = 1 x 10(-4)). When analyzed in all subjects (n = 5531), rs2470152 was clearly associated with both E2 (P = 2 x 10(-14)) and E1 (P = 8 x 10(-19)) levels. In addition, this polymorphism was modestly associated with lumbar spine BMD (P &lt; 0.01) and prevalent self-reported fractures (P &lt; 0.05). Conclusions: rs2470152 of the CYP19 gene is clearly associated with serum E2 and E1 levels in men. (J Clin Endocrinol Metab 94: 1033-1041, 2009)},
  author       = {Eriksson, Anna L. and Lorentzon, Mattias and Vandenput, Liesbeth and Labrie, Fernand and Lindersson, Marie and Syvanen, Ann-Christine and Orwoll, Eric S. and Cummings, Steven R. and Zmuda, Joseph M. and Ljunggren, Osten and Karlsson, Magnus and Mellstrom, Dan and Ohlsson, Claes},
  issn         = {1945-7197},
  language     = {eng},
  number       = {3},
  pages        = {1033--1041},
  publisher    = {The Endocrine Society},
  series       = {Journal of Clinical Endocrinology and Metabolism},
  title        = {Genetic Variations in Sex Steroid-Related Genes as Predictors of Serum Estrogen Levels in Men},
  url          = {http://dx.doi.org/10.1210/jc.2008-1283},
  volume       = {94},
  year         = {2009},
}