Associations of SRD5A1 gene variants and testosterone with dysglycemia: Henan Rural Cohort study
Associations of SRD5A1 gene variants and testosterone with dysglycemia: Henan Rural Cohort study
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SRD5A1 基因变异和睾酮与血糖异常的关联：河南农村队列研究
DOI：
10.1016/j.numecd.2019.11.011
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
Mao Zhenxing
中科院分区：
文献类型：
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作者：
Liu Xue;Wei D;an;Jiang Jingjing;Liu Xiaotian;Tu Runqi;Luo Zhicheng;Wang Yan;Dong Xiaokang;Qiao Dou;Shen Fang;Li Ruiying;Wang Yikang;Jin Yuxi;Yu Songcheng;Huo Wenqian;Li Linlin;Li Wenjie;Jing Tao;Wang Chongjian;Mao Zhenxing
摘要（#br）背景和目的（#br）多项研究支持睾酮和2型糖尿病（T2 DM）之间的复杂关系，睾酮的转化受几种还原酶的影响。因此，我们的目的是探讨类固醇-5 α-还原酶1型（SRD 5A 1）基因多态性与空腹血糖受损（IFG）和2型糖尿病的关系，以及睾酮和基因型对糖代谢的交互作用。（#br）方法和结果（#br）进行了包括2365名参与者的病例对照研究。从全血中提取基因组DNA，并对SRD 5A 1单核苷酸多态性（SNP）rs 1691053进行基因分型。采用多因素Logistic回归和线性回归分析SRD 5A 1 rs 1691053等位基因和基因型与糖代谢的相关性。应用广义线性模型研究了血清睾酮对男性糖代谢指标的调节作用。（#br）多变量校正后，男性携带者中IFG纯合子CC基因型的比值比（OR）为2.62（95%CI：1.11-6.18）。此外，在男性中观察到SRD 5A 1 rs 1691053多态性与糖代谢不良指数的显著相关性。有趣的是，在女性中观察到相反的关联。发现SNP与睾酮之间存在交互作用，突变更可能导致不利的代谢表型。（#br）结论（#br）SRD 5A 1 rs 1691053基因多态性与糖代谢紊乱独立相关。SRD 5A 1基因多态性和睾酮之间的相互作用涉及糖代谢在男性中被确定。虽然这一初步数据应该与其他严格的研究重复，但它强调了SNP-睾酮相互作用对糖皮质激素的重要性。
Abstract(#br)Background and aim(#br)Multiple studies support a complex relationship between testosterone and type 2 diabetes mellitus (T2DM) and the transformation of testosterone is affected by several reductases. Thus, we aimed to explore the associations of steroid-5α-reductase type 1 ( SRD5A1 ) gene polymorphism with impaired fasting glucose (IFG) and T2DM and the interactive effects of testosterone and genotypes on glycometabolism.(#br)Methods and results(#br)A case–control study including 2365 participants was performed. Genomic DNA was extracted from the whole blood and genotyped for the SRD5A1 single nucleotide polymorphisms (SNP) rs1691053. Multivariable logistic regression and linear regression were performed to estimate the associations of SRD5A1 rs1691053 alleles and genotypes with glycometabolism. Generalized linear models were used to investigate the modulatory effects of serum testosterone on glycometabolism indexes in males.(#br)After multivariable adjustment, the odds ratio ( OR ) of homozygous CC genotypes in male carriers was 2.62 (95% CI : 1.11–6.18) for IFG. Furthermore, significant associations of SRD5A1 rs1691053 polymorphisms with adverse indices of glycometabolism were observed in males. Interestingly, the opposite associations in females were observed. The interactive associations of SNP and testosterone were found and mutations were more likely to lead unfavorable metabolic phenotypes.(#br)Conclusion(#br)These results showed that SRD5A1 rs1691053 gene polymorphism was independently associated with glycometabolism. The interaction between a genetic polymorphism from SRD5A1 and testosterone involved glycometabolism was identified in males. Although this preliminary data should be replicated with other rigorous researches, it highlighted the importance of the SNP-testosterone interaction over the present of glycometabolism.