title: Genetic variations in sex steroid-related genes as predictors of serum estrogen levels in men.
abstract: 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.
authors.affiliation: Center for Bone Research at the Sahlgrenska Academy, Department of Internal Medicine Gothenburg University, SE-413 45 Gothenburg, Sweden.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Eriksson
authors.forename: Mattias
authors.initials: M
authors.lastname: Lorentzon
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Vandenput
authors.forename: Fernand
authors.initials: F
authors.lastname: Labrie
authors.forename: Marie
authors.initials: M
authors.lastname: Lindersson
authors.forename: Ann-Christine
authors.initials: AC
authors.lastname: Syvänen
authors.forename: Eric S
authors.initials: ES
authors.lastname: Orwoll
authors.forename: Steven R
authors.initials: SR
authors.lastname: Cummings
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Zmuda
authors.forename: Osten
authors.initials: O
authors.lastname: Ljunggren
authors.forename: Magnus K
authors.initials: MK
authors.lastname: Karlsson
authors.forename: Dan
authors.initials: D
authors.lastname: Mellström
authors.forename: Claes
authors.initials: C
authors.lastname: Ohlsson
mesh_terms: 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
chemical_list: D004970:Estrone; D013739:Testosterone; D004958:Estradiol; D001141:Aromatase