Genetic variations in sex steroid-related genes as predictors of serum estrogen levels in men

Anna L. Eriksson, Mattias Lorentzon, Liesbeth Vandenput, Fernand Labrie, Marie Lindersson, Ann Christine Syvänen, Eric Orwoll, Steven R. Cummings, Joseph M. Zmuda, Östen Ljunggren, Magnus K. Karlsson, Dan Mellström, Claes Ohlsson

Research output: Contribution to journalArticle

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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 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.

Original languageEnglish (US)
Pages (from-to)1033-1041
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Volume94
Issue number3
DOIs
StatePublished - Mar 2009

Fingerprint

Aromatase
Estrogens
Genes
Polymorphism
Steroids
Serum
Osteoporosis
Testosterone
Nucleotides
Sweden
Single Nucleotide Polymorphism
Estrone
Biosynthesis
Obesity
Gas chromatography
Introns
Breast Neoplasms
Mass spectrometry
Estradiol
Screening

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

Cite this

Eriksson, A. L., Lorentzon, M., Vandenput, L., Labrie, F., Lindersson, M., Syvänen, A. C., ... Ohlsson, C. (2009). Genetic variations in sex steroid-related genes as predictors of serum estrogen levels in men. Journal of Clinical Endocrinology and Metabolism, 94(3), 1033-1041. https://doi.org/10.1210/jc.2008-1283

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; Syvänen, Ann Christine; Orwoll, Eric; Cummings, Steven R.; Zmuda, Joseph M.; Ljunggren, Östen; Karlsson, Magnus K.; Mellström, Dan; Ohlsson, Claes.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 94, No. 3, 03.2009, p. 1033-1041.

Research output: Contribution to journalArticle

Eriksson, AL, Lorentzon, M, Vandenput, L, Labrie, F, Lindersson, M, Syvänen, AC, Orwoll, E, Cummings, SR, Zmuda, JM, Ljunggren, Ö, Karlsson, MK, Mellström, D & Ohlsson, C 2009, 'Genetic variations in sex steroid-related genes as predictors of serum estrogen levels in men', Journal of Clinical Endocrinology and Metabolism, vol. 94, no. 3, pp. 1033-1041. https://doi.org/10.1210/jc.2008-1283
Eriksson, Anna L. ; Lorentzon, Mattias ; Vandenput, Liesbeth ; Labrie, Fernand ; Lindersson, Marie ; Syvänen, Ann Christine ; Orwoll, Eric ; Cummings, Steven R. ; Zmuda, Joseph M. ; Ljunggren, Östen ; Karlsson, Magnus K. ; Mellström, Dan ; Ohlsson, Claes. / Genetic variations in sex steroid-related genes as predictors of serum estrogen levels in men. In: Journal of Clinical Endocrinology and Metabolism. 2009 ; Vol. 94, No. 3. pp. 1033-1041.
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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 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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AU - Eriksson, Anna L.

AU - Lorentzon, Mattias

AU - Vandenput, Liesbeth

AU - Labrie, Fernand

AU - Lindersson, Marie

AU - Syvänen, Ann Christine

AU - Orwoll, Eric

AU - Cummings, Steven R.

AU - Zmuda, Joseph M.

AU - Ljunggren, Östen

AU - Karlsson, Magnus K.

AU - Mellström, Dan

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