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Articles by F. W. K Chan
Total Records ( 1 ) for F. W. K Chan
  J Jiang , N. L. S Tang , C Ohlsson , A. L Eriksson , L Vandenput , C Liao , X Wang , F. W. K Chan , A Kwok , E Orwoll , T. C. Y Kwok , J Woo and P. C. Leung
  BACKGROUND:

Results of recent studies have demonstrated that genetic variants of the enzyme steroid 5 reductase type II (SRD5A2) are associated with serum concentrations of major androgen metabolites such as conjugates of androstane-3,17β-diol-glucuronide (3-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-3,l7β-diol-3-glucuronide (3-diol-3G) and androstane-3,17β-diol-17-glucuronide (3-diol-17G).

METHODS:

We used GC-MS and LC-MS to measure serum sex steroid concentrations, including testosterone and dihydrotestosterone, and 3-diol-3G and 3-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 3-diol-17G concentration (P = 0.040). On the other hand, SNP rs12470143 was found to be significantly correlated with 3-diol-3G concentration (P = 0.021). Results of haplotype analysis suggested that the presence of an A-C-G haplotype leads to an increased 3-diol-3G concentration, a finding consistent with results of single SNP analysis.

CONCLUSIONS:

The genetic variation of SRD5A2 is associated with circulating 3-diol-3G and 3-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 3-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 3-diol-G.

 
 
 
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