title: Association of SRD5A2 variants and serum androstane-3alpha,17beta-diol glucuronide concentration in Chinese elderly men.
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 to measure 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.
authors.affiliation: Department of Chemical Pathology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
authors.forename: Jieying
authors.initials: J
authors.lastname: Jiang
authors.forename: Nelson L S
authors.initials: NL
authors.lastname: Tang
authors.forename: Claes
authors.initials: C
authors.lastname: Ohlsson
authors.forename: Anna L
authors.initials: AL
authors.lastname: Eriksson
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Vandenput
authors.forename: ChenDi
authors.initials: C
authors.lastname: Liao
authors.forename: Xingyan
authors.initials: X
authors.lastname: Wang
authors.forename: Frank W K
authors.initials: FW
authors.lastname: Chan
authors.forename: Anthony
authors.initials: A
authors.lastname: Kwok
authors.forename: Eric
authors.initials: E
authors.lastname: Orwoll
authors.forename: Timothy C Y
authors.initials: TC
authors.lastname: Kwok
authors.forename: Jean
authors.initials: J
authors.lastname: Woo
authors.forename: Ping Chung
authors.initials: PC
authors.lastname: Leung
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics*; D000368:Aged; D015113:Androstane-3,17-diol / Q000031:analogs & derivatives* / Q000097:blood; D044466:Asian People; D002849:Chromatography, Gas; D002853:Chromatography, Liquid; D013196:Dihydrotestosterone / Q000097:blood; D006239:Haplotypes; D006723:Hong Kong; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D013058:Mass Spectrometry; D008565:Membrane Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D013739:Testosterone / Q000097:blood
chemical_list: D008565:Membrane Proteins; D012738:Sex Hormone-Binding Globulin; D013196:Dihydrotestosterone; D015113:Androstane-3,17-diol; C028895:androstane-3,17-diol glucuronide; D013739:Testosterone; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C548468:SRD5A2 protein, human