台灣老化男性之肝细胞核因子4α P2 啟動子基因變異與罹患代謝症候群及睪固酮低下風險相關
劉家駒1-3, 李永進1,2,4, 黃書彬1,2, 鄭凱鴻5, 謝翠娟6-7, 黃琮懿1, 李政學1, 耿俊閎4,
李經家1,2,吳文正1,2,8
高雄醫學大學附設醫院 泌尿科1
高雄醫學大學 醫學院 醫學系 泌尿學科2
衛生福利部 屏東醫院 泌尿科3
高雄市立小港醫院(委託財團法人高雄醫學大學經營) 泌尿科4
高雄醫學大學 內科部 心臟內科5
高雄學大學 醫學院 醫學研究所6
高雄醫學大學 環境醫學研究中心7
高雄市立大同醫院(委託財團法人高雄醫學大學經營) 泌尿科8
Hepatocyte nuclear factor 4 alpha P2 promoter variants associate with the risk of metabolic syndrome and testosterone deficiency in aging Taiwanese men
Chia-Chu Liu1-3, Yung-Chin Lee1,2,4, Shu-Pin Huang1,2, Kai-Hung Cheng5, Tusty-Jiuan Hsieh6,7, Tsung-Yi Huang1, Cheng-Hsueh Lee1, Jiun-Hung Geng4, Ching-Chia Li1,2, Wen-Jeng Wu1,2,8
1Department of Urology, Kaohsiung Medical University Hospital; Department of Urology
2Faculty of Medicine, College of Medicine, Kaohsiung Medical University
3Department of Urology, Pingtung Hospital, Ministry of Health and Welfare
4Department of Urology, Kaohsiung Municipal Hsiao-Kang Hospital
5Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital
6Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University
7Research Center for Environmental Medicine, Kaohsiung Medical University
8Department of Urology, Kaohsiung Municipal Ta-Tung Hospital
Purpose: Metabolic syndrome (MetS) and testosterone deficiency (TD) are two closely linked diseases commonly found among aging men. Insulin resistance is postulated to be an important link between the two. Because hepatocyte nuclear factor 4 alpha (HNF4A) can regulate gene expression and insulin secretion in pancreatic β cells, single-nucleotide polymorphisms (SNPs) of HNF4A may increase the risk of both MetS and TD in men. Therefore, we investigated the relationship between SNPs of HNF4A and the risk of developing MetS and TD in a population of aging Taiwanese men.
Materials and Methods: A health screening of men over 40 years of age was conducted free of charge by a medical center in Kaohsiung City, Taiwan. All participants received a physical examination, answered a questionnaire, and provided a 20 cc sample of whole blood for purposes of biochemical and genetic evaluation. Serum albumin, total testosterone (TT), and sex hormone-binding globulin levels were measured. Free testosterone level was calculated. Three common SNPs (rs11574736, rs1884613, and rs2144908) of HNF4A were selected and identified using a TaqMan 5’ allelic discrimination assay
Results: A total of five hundred and fifty-nine men were enrolled for this study (mean age: 55.8±4.9 years). Prevalence of TD was significantly higher (p=0.031) in subjects with MetS (16.8%) than those without MetS (10.1%). In SNP rs1884613 of HNF4A, subjects with the C allele carried a 1.31 and 1.50 times higher risk of developing MetS and TD, respectively, compared to those with the G allele, after adjusting for potential covariates. In addition, subjects with the CC genotype were exposed to a 1.91 and 2.20 times higher risk of developing MetS and TD, respectively, compared to those with the GG genotype.
Conclusion: The rs1884613 SNP marker of HNF4A may be significantly associated with an increased risk for developing both MetS and TD in aging Taiwanese men. Our findings may point to the importance of the role played by insulin resistance in the link between MetS and TD. Further population-based studies utilizing larger samples of different ethnicities may be needed to confirm these preliminary results.