Association of SRD5A2 variants and serum androstane-3α,17β-diol glucuronide concentration in Chinese elderly men

Jieying Jiang, Nelson L.S. Tang, Claes Ohlsson, Anna L. Eriksson, Liesbeth Vandenput, Chen Di Liao, Xingyan Wang, Frank W.K. Chan, Anthony Kwok, Eric Orwoll, Timothy C.Y. Kwok, Jean Woo, Ping Chung Leung

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Abstract

BACKGROUND: Results of recent studies have demonstrated that genetic variants of the enzyme steroid 5α reductase type II (SRD5A2) are associated with serum concentrations of major androgen metabolites such as conjugates of androstane-3α,17β-diol-glucuronide (3α-diol-G). However, this association was not consistently 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-3α,l7β-diol-3-glucuronide (3α-diol-3G) and androstane-3α,17β-diol-17-glucuronide (3α-diol-17G). METHODS: We used GC-MS and LC-MS tomeasure serum sex steroid concentrations, including testosterone and dihydrotestosterone, and 3α-diol-3G and 3α-diol-17G in 1182 Chinese elderly men age 65 and older. Genotyping of the 3 SRD5A2 tagSNPs [rs3731586, rs12470143, and rs523349 (V89L)] was performed by using melting-temperature-shift allele-specific PCR. RESULTS: The well-described SRD5A2 missense variant rs523349 (V89L) was modestly associated with the 3α-diol-17G concentration (P = 0.040). On the other hand, SNP rs12470143 was found to be significantly correlated with 3α-diol-3G concentration (P = 0.021). Results of haplotype analysis suggested that the presence of an A-C-G haplotype leads to an increased 3α-diol-3G concentration, a finding consistent with results of single SNP analysis. CONCLUSIONS: The genetic variation of SRD5A2 is associated with circulating 3α-diol-3G and 3α-diol-17G concentrations in Chinese elderly men. In addition, we showed that SRD5A2 haplotypic association, rather than a single SNP alone, might be a better predictor of the 3α-diol-G concentration. Thus, the effect of either the haplotype itself or of other ungenotyped SNPs in linkage disequilibrium with the haplotype is responsible for the interindividual variation of 3α-diol-G.

Original languageEnglish (US)
Pages (from-to)1742-1749
Number of pages8
JournalClinical chemistry
Volume56
Issue number11
DOIs
StatePublished - Nov 1 2010

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ASJC Scopus subject areas

  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Jiang, J., Tang, N. L. S., Ohlsson, C., Eriksson, A. L., Vandenput, L., Liao, C. D., Wang, X., Chan, F. W. K., Kwok, A., Orwoll, E., Kwok, T. C. Y., Woo, J., & Leung, P. C. (2010). Association of SRD5A2 variants and serum androstane-3α,17β-diol glucuronide concentration in Chinese elderly men. Clinical chemistry, 56(11), 1742-1749. https://doi.org/10.1373/clinchem.2010.150607