Department of Chemical Pathology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
Clin Chem. 2010 Nov;56(11):1742-9. doi: 10.1373/clinchem.2010.150607. Epub 2010 Sep 20.
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).
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.
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.
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.
最近的研究结果表明，甾体 5α 还原酶 II 型（SRD5A2）酶的遗传变异与主要雄激素代谢物如雄烷-3α，17β-二醇-葡萄糖醛酸苷（3α-二醇-G）的缀合物的血清浓度相关。然而，这种关联在不同种族群体中并不一致。因此，我们旨在通过检查 2 种代谢物缀合物：雄烷-3α，17β-二醇-3-葡萄糖醛酸苷（3α-二醇-3G）和雄烷-3α，17β-二醇-17-葡萄糖醛酸苷（3α-二醇-17G），来确定这种与 SRD5A2 遗传变异的关联是否存在于中国老年男性队列中。
我们使用 GC-MS 和 LC-MS 测量了 1182 名年龄在 65 岁及以上的中国老年男性的血清性激素浓度，包括睾酮和二氢睾酮，以及 3α-二醇-3G 和 3α-二醇-17G。通过熔解温度-移峰等位基因特异性 PCR 对 3 个 SRD5A2 标签 SNP [rs3731586、rs12470143 和 rs523349（V89L）]进行基因分型。
描述良好的 SRD5A2 错义变体 rs523349（V89L）与 3α-二醇-17G 浓度呈适度相关（P=0.040）。另一方面，SNP rs12470143 与 3α-二醇-3G 浓度显著相关（P=0.021）。单体型分析结果表明，A-C-G 单体型的存在导致 3α-二醇-3G 浓度增加，这与单个 SNP 分析的结果一致。
SRD5A2 的遗传变异与中国老年男性的循环 3α-二醇-3G 和 3α-二醇-17G 浓度相关。此外，我们表明，SRD5A2 单体型关联而不是单个 SNP 本身可能是 3α-二醇-G 浓度的更好预测因子。因此，单体型本身或与单体型连锁不平衡的其他未分型 SNP 的作用负责 3α-二醇-G 的个体间变异。
