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Twin studies suggest a heritable component to circulating sex steroid hormones and sex hormone-binding globulin (SHBG). In the NCI-Breast and Prostate Cancer Cohort Consortium, 874 SNPs in 37 candidate genes in the sex steroid hormone pathway were examined in relation to circulating levels of SHBG (N = 4720), testosterone (N = 4678), 3 alpha-androstanediol-glucuronide (N = 4767) and 17beta-estradiol (N = 2014) in Caucasian men. rs1799941 in SHBG is highly significantly associated with circulating levels of SHBG (P = 4.52 x 10(-21)), consistent with previous studies, and testosterone (P = 7.54 x 10(-15)), with mean difference of 26.9 and 14.3%, respectively, comparing wild-type to homozygous variant carriers. Further noteworthy novel findings were observed between SNPs in ESR1 with testosterone levels (rs722208, mean difference = 8.8%, P = 7.37 x 10(-6)) and SRD5A2 with 3 alpha-androstanediol-glucuronide (rs2208532, mean difference = 11.8%, P = 1.82 x 10(-6)). Genetic variation in genes in the sex steroid hormone pathway is associated with differences in circulating SHBG and sex steroid hormones.

Original publication

DOI

10.1093/hmg/ddp302

Type

Journal article

Journal

Hum Mol Genet

Publication Date

01/10/2009

Volume

18

Pages

3749 - 3757

Keywords

3-Oxo-5-alpha-Steroid 4-Dehydrogenase, Adult, Aged, Aged, 80 and over, Case-Control Studies, Cohort Studies, Estrogen Receptor alpha, European Continental Ancestry Group, Gonadal Steroid Hormones, Humans, Male, Middle Aged, Prostatic Neoplasms, Quantitative Trait Loci, Sex Hormone-Binding Globulin