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


METHODS
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.
Eriksson
Anna L
AL
Center for Bone Research at the Sahlgrenska Academy, Department of Internal Medicine Gothenburg University, SE-413 45 Gothenburg, Sweden.
Lorentzon
Mattias
M
Vandenput
Liesbeth
L
Labrie
Fernand
F
Lindersson
Marie
M
Syvänen
Ann-Christine
AC
Orwoll
Eric S
ES
Cummings
Steven R
SR
Zmuda
Joseph M
JM
Ljunggren
Osten
O
Karlsson
Magnus K
MK
Mellström
Dan
D
Ohlsson
Claes
C
D000293:Adolescent; D000328:Adult; D001141:Aromatase / Q000235:genetics*; D015519:Bone Density; D015331:Cohort Studies; D004958:Estradiol / Q000097:blood*; D004970:Estrone / Q000097:blood*; D006801:Humans; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D013739:Testosterone / Q000097:blood
D004970:Estrone; D013739:Testosterone; D004958:Estradiol; D001141:Aromatase