Xue Liu1, Dandan Wei1, Jingjing Jiang1, Xiaotian Liu1, Runqi Tu1, Zhicheng Luo1, Yan Wang1, Xiaokang Dong1, Dou Qiao1, Fang Shen2, Ruiying Li1, Yikang Wang1, Yuxi Jin3, Songcheng Yu2, Wenqian Huo4, Linlin Li1, Wenjie Li2, Tao Jing5, Chongjian Wang1, Zhenxing Mao6. 1. Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, PR China. 2. Department of Nutrition and Food Hygiene, College of Public Health, Zhengzhou University, Zhengzhou, Henan, PR China. 3. Academy of Medical Science, Zhengzhou University, Zhengzhou, Henan, PR China; Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, PR China. Electronic address: jinyuxi1303@163.com. 4. Department of Occupational and Environmental Health Sciences, College of Public Health, Zhengzhou University, Zhengzhou, Henan, PR China. 5. State Key Laboratory of Environment Health (Incubation), Key Laboratory of Environment and Health, Ministry of Education, Key Laboratory of Environment and Health (Wuhan), Ministry of Environmental Protection, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, PR China. 6. Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, PR China. Electronic address: maozhr@gmail.com.
Abstract
BACKGROUND AND AIM: 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. METHODS AND RESULTS: 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. 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. CONCLUSION: 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.
BACKGROUND AND AIM: 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. METHODS AND RESULTS: 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 SRD5A1rs1691053 alleles and genotypes with glycometabolism. Generalized linear models were used to investigate the modulatory effects of serum testosterone on glycometabolism indexes in males. 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 SRD5A1rs1691053 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. CONCLUSION: These results showed that SRD5A1rs1691053 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.