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J Clin Endocrinol Metab. 2009 Mar;94(3):1033-41. doi: 10.1210/jc.2008-1283. Epub 2008 Dec 30.

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

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1
Center for Bone Research at the Sahlgrenska Academy, Department of Internal Medicine Gothenburg University, SE-413 45 Gothenburg, Sweden.

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 < 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.

PMID:
19116238
PMCID:
PMC2681277
DOI:
10.1210/jc.2008-1283
[Indexed for MEDLINE]
Free PMC Article
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