Association of SRD5A2 Variants and Serum Androstane-3 (cid:1) ,17 (cid:2) -Diol Glucuronide Concentration in Chinese Elderly Men

BACKGROUND : Results of recent studies have demon-strated that genetic variants of the enzyme steroid 5 (cid:1) reductase type II (SRD5A2) are associated with serum concentrations of major androgen metabolites such as conjugates of androstane-3 (cid:1) ,17 (cid:2) -diol-glucuronide (3 (cid:1) -diol-G). However, this association was not consis-tently found among different ethnic groups. Thus, we aimed to determine whether the association with SRD5A2 genetic variations exists in a cohort of healthy Chinese elderly men, by examining 2 metabolite conjugates: androstane-3 (cid:1) ,l7 (cid:2) -diol-3-glucuronide (3 (cid:1) -diol-3G) and androstane-3 (cid:1) ,17 (cid:2) -diol-17-glucuronide (3 (cid:1) -diol-17G). METHODS : We used GC-MS and LC-MS to measure serum sex steroid concentrations, including testosterone and dihydrotestosterone, and 3 (cid:1) -diol-3G and 3 (cid:1) -diol-17G in 1182 Chinese elderly men age 65 and older. Genotyping of the 3 SRD5A2 tagSNPs [rs3731586, rs12470143, and rs523349 (V89L)]

[1]  J. Woo,et al.  Association of genetic variations in aromatase gene with serum estrogen and estrogen/testosterone ratio in Chinese elderly men. , 2010, Clinica chimica acta; international journal of clinical chemistry.

[2]  A. Meikle.  Genetic Variations in Sex Steroid-Related Genes as Predictors of Serum Estrogen Levels in Men , 2010 .

[3]  A. Singleton,et al.  Genomewide association studies and human disease. , 2009, The New England journal of medicine.

[4]  M. Thun,et al.  Quantitative trait loci predicting circulating sex steroid hormones in men from the NCI-Breast and Prostate Cancer Cohort Consortium (BPC3). , 2009, Human molecular genetics.

[5]  P. O’Reilly,et al.  Genome-wide association study identifies eight loci associated with blood pressure , 2009, Nature Genetics.

[6]  E. Demerath,et al.  Meta-analysis of genome-wide association data identifies two loci influencing age at menarche , 2009, Nature Genetics.

[7]  B. Yeap.  Testosterone and ill-health in aging men , 2009, Nature Clinical Practice Endocrinology &Metabolism.

[8]  Christian Gieger,et al.  Six new loci associated with body mass index highlight a neuronal influence on body weight regulation , 2009, Nature Genetics.

[9]  L. Lönn,et al.  Androgens and glucuronidated androgen metabolites are associated with metabolic risk factors in men. , 2007, The Journal of clinical endocrinology and metabolism.

[10]  D. Posthuma,et al.  Heritability of reproductive hormones in adult male twins. , 2007, Human reproduction.

[11]  D. English,et al.  5α‐Reductase type 2 gene variant associations with prostate cancer risk, circulating hormone levels and androgenetic alopecia , 2007, International journal of cancer.

[12]  S. Olson,et al.  Variants in estrogen biosynthesis genes, sex steroid hormone levels, and endometrial cancer: a HuGE review. , 2007, American journal of epidemiology.

[13]  Claes Ohlsson,et al.  Serum Levels of Specific Glucuronidated Androgen Metabolites Predict BMD and Prostate Volume in Elderly Men , 2006, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[14]  D. English,et al.  Circulating Steroid Hormones and the Risk of Prostate Cancer , 2006, Cancer Epidemiology Biomarkers & Prevention.

[15]  Karen Chuang,et al.  High-throughput SNP genotyping by single-tube PCR with Tm-shift primers. , 2005, BioTechniques.

[16]  D. Carmelli,et al.  Heritability of plasma sex hormones and hormone binding globulin in adult male twins. , 2005, The Journal of clinical endocrinology and metabolism.

[17]  R. Altman,et al.  Finding haplotype tagging SNPs by use of principal components analysis. , 2004, American journal of human genetics.

[18]  B. Horne,et al.  Principal component analysis for selection of optimal SNP‐sets that capture intragenic genetic variation , 2004, Genetic epidemiology.

[19]  Z. Meng,et al.  Selection of genetic markers for association analyses, using linkage disequilibrium and haplotypes. , 2003, American journal of human genetics.

[20]  T. Habuchi,et al.  Association of V89L SRD5A2 polymorphism with prostate cancer development in a Japanese population. , 2003, The Journal of urology.

[21]  T. Key,et al.  Association between two polymorphisms in the SRD5A2 gene and serum androgen concentrations in British men. , 2003, Cancer Epidemiology, Biomarkers and Prevention.

[22]  J. Reichardt,et al.  Hormones and prostate cancer: Current perspectives and future directions , 2002, The Prostate.

[23]  F. Mostofi,et al.  Polymorphic markers in the SRD5A2 gene and prostate cancer risk: a population-based case-control study. , 2001, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[24]  P. Donnelly,et al.  A new statistical method for haplotype reconstruction from population data. , 2001, American journal of human genetics.

[25]  M. Forrest,et al.  The association between polymorphisms in the CYP17 and 5alpha-reductase (SRD5A2) genes and serum androgen concentrations in men. , 2001, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[26]  C. J. Chen,et al.  Androgen-receptor gene CAG repeats, plasma testosterone levels, and risk of hepatitis B-related hepatocellular carcinoma. , 2000, Journal of the National Cancer Institute.

[27]  R Higuchi,et al.  Single-tube genotyping without oligonucleotide probes. , 1999, Genome research.

[28]  M. Pike,et al.  A prevalent missense substitution that modulates activity of prostatic steroid 5alpha-reductase. , 1997, Cancer research.