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Cited by 8Hormonal and reproductive studiesSperm and Testicular FunctionHypothalamic control of reproductive hormones

Effects of SHBG rs1799941 Polymorphism on Free Testosterone Levels and Hypogonadism Risk in Young Non-Diabetic Obese Males

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Castellano-Castillo, Daniel, Royo, José Luis, Martínez-Escribano, Ana, Sánchez-Alcoholado, Lidia, Molina-Vega, María, Queipo-Ortuño, María Isabel, Ruiz-Galdon, Maximiliano, J. Álvarez-Millán, Juan +5 more·2019·Journal of Clinical Medicine
DOI 10.3390/jcm8081136PMC PMC6722847
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Abstract

Introduction: Obesity has been associated with increased risk of presenting hypogonadism. Free testosterone (FT) is the fraction of testosterone that carries out the biological function of testosterone, and is determined from total testosterone (TT) and sex-hormone binding globulin (SHBG) levels. We aimed to study the SHBG polymorphism rs1799941 in a cohort of young non-diabetic obese males to unravel the possible implication of this polymorphism in obesity-related hypogonadism. Methodology: 212 young (<45 years) non-diabetic obese (BMI ≥ 30 kg/m2) males participated in this study. Subjects were classified according to TT and FT levels in: Eugonadal (n = 55, TT > 3.5 ng/mL and FT ≥ 70 pg/mL; EuG), normal FT hypogonadism (n = 40, TT < 3.5 and FT ≥ 70 pg/mL; normal FT HG) and hypogonadism (n = 117, TT < 3.5 ng/mL and TL < 70 pg/mL; HG). The SHBG rs1799941 polymorphism (GG/GA/AA) was analyzed using the Taqman Open Array (Applied biosystem). Results: The rs1799941 frequencies were different among the groups. Higher proportion of the allele (A) was found in HG, compared to EuG and normal FT HG. Among the genotypes, the rare homozygous (AA) were found in the normal FT HG group and higher levels of serum SHBG and lower of FT were observed. The presence of the allele A was related (according to lineal regression models) to an increased of SHBG levels ((GA) β = 3.28; (AA) β = 12.45) and a decreased of FT levels ((GA) β = −9.19; (AA) β = −18.52). The presence of the allele (A) increased the risk of presenting HG compared to normal FT HG (OR = 2.54). Conclusions: The rs1799941 of the SHBG gene can partially determine the presence of obesity-related hypogonadism in young non-diabetic males and whether these subjects have normal FT HG.

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Research works printed but not linked: 27

  1. [1]Bardou M. Barkun A.N. Martel M. Republished: Obesity and Colorectal Cancer Postgrad. Med. J. 2013 89 519 533 10.1136/postgradmedj-2013-304701rep 23955330 · DOI
  2. [2]Grossmann M. Hypogonadism and Male Obesity: Focus on Unresolved Questions Clin. Endocrinol. 2018 10.1111/cen.13723 29683196 · DOI · Paper page
  3. [3]Ventimiglia E. Ippolito S. Capogrosso P. Pederzoli F. Cazzaniga W. Boeri L. Cavarretta I. Alfano M. Viganò P. Montorsi F. Primary, Secondary and Compensated Hypogonadism: A Novel Risk Stratification for Infertile Men Andrology 2017 5 505 510 10.1111/andr.12335 28409903 · DOI
  4. [4]Maggio M. Basaria S. Welcoming Low Testosterone as a Cardiovascular Risk Factor Int. J. Impot. Res. 2009 21 261 264 10.1038/ijir.2009.25 19536127 PMC2834340 · DOI
  5. [5]Li H. Pham T. Mcwhinney B.C. Ungerer J.P. Pretorius C.J. Richard D.J. Mortimer R.H. Emden M.C. Richard K. Sex Hormone Binding Globulin Modifies Testosterone Action and Metabolism in Prostate Cancer Cells Int. J. Endocrinol. 2016 2016 1 10 10.1155/2016/6437585 PMC5136390 27990161 · DOI · Paper page
  6. [6]Tint A.N. Hoermann R. Wong H. Ekinci E.I. Macisaac R.J. Jerums G. Zajac J.D. Grossmann M. Association of Sex Hormone-Binding Globulin and Free Testosterone with Mortality in Men with Type 2 Diabetes Mellitus Eur. J. Endocrinol. 2016 174 59 68 10.1530/EJE-15-0672 26483395 · DOI
  7. [7]Firtser S. Juonala M. Magnussen C.G. Jula A. Loo B.M. Marniemi J. Viikari J.S.A. Toppari J. Perheentupa A. Hutri-Kähönen N. Relation of Total and Free Testosterone and Sex Hormone-Binding Globulin with Cardiovascular Risk Factors in Men Aged 24-45 Years. The Cardiovascular Risk in Young Finns Study Atherosclerosis 2012 222 257 262 10.1016/j.atherosclerosis.2012.02.020 22420889 · DOI
  8. [8]Hammond G.L. Molecular Properties of Corticosteroid Binding Globulin and the Sex-Steroid Binding Proteins Endocr. Rev. 1990 11 65 79 10.1210/edrv-11-1-65 2180688 · DOI
  9. [9]Ahn J. Schumacher F.R. Berndt S.I. Pfeiffer R. Albanes D. Andriole G.L. Ardanaz E. Boeing H. Bueno-de-Mesquita B. Chanock S.J. Quantitative Trait Loci Predicting Circulating Sex Steroid Hormones in Men from the NCI-Breast and Prostate Cancer Cohort Consortium (BPC3) Hum. Mol. Genet. 2009 18 3749 3757 10.1093/hmg/ddp302 19574343 PMC2742399 · DOI · Paper page
  10. [10]Nenonen H.A. Giwercman A. Hallengren E. Giwercman Y.L. Non-Linear Association between Androgen Receptor CAG Repeat Length and Risk of Male Subfertility-a Meta-Analysis Int. J. Androl. 2011 34 327 332 10.1111/j.1365-2605.2010.01084.x 20579136 · DOI
  11. [11]Nenonen H. Björk C. Skjaerpe P.-A. Giwercman A. Rylander L. Svartberg J. Giwercman Y.L. CAG Repeat Number Is Not Inversely Associated with Androgen Receptor Activity in Vitro Mol. Hum. Reprod. 2010 16 153 157 10.1093/molehr/gap097 19884136 · DOI
  12. [13]Coviello A.D. Haring R. Wellons M. Vaidya D. Lehtimäki T. Keildson S. Lunetta K.L. He C. Fornage M. Lagou V. A Genome-Wide Association Meta-Analysis of Circulating Sex Hormone-Binding Globulin Reveals Multiple Loci Implicated in Sex Steroid Hormone Regulation PLoS Genet. 2012 8 10.1371/journal.pgen.1002805 22829776 PMC3400553 · DOI · Paper page
  13. [14]Cangiano B. Duminuco P. Vezzoli V. Guizzardi F. Chiodini I. Corona G. Maggi M. Persani L. Bonomi M. Evidence for a Common Genetic Origin of Classic and Milder Adult-Onset Forms of Isolated Hypogonadotropic Hypogonadism J. Clin. Med. 2019 8 126 10.3390/jcm8010126 30669598 PMC6352096 · DOI
  14. [15]Eriksson A.L. Lorentzon M. Mellström D. Vandenput L. Swanson C. Andersson N. Hammond G.L. Jakobsson J. Rane A. Orwoll E.S. SHBG Gene Promoter Polymorphisms in Men Are Associated with Serum Sex Hormone-Binding Globulin, Androgen and Androgen Metabolite Levels, and Hip Bone Mineral Density J. Clin. Endocrinol. Metab. 2006 91 5029 5037 10.1210/jc.2006-0679 16926255 · DOI · Paper page
  15. [16]Peter A. Kantartzis K. Machann J. Schick F. Staiger H. Machicao F. Schleicher E. Fritsche A. Häring H.U. Stefan N. Relationships of Circulating Sex Hormone-Binding Globulin with Metabolic Traits in Humans Diabetes 2010 59 3167 3173 10.2337/db10-0179 20841609 PMC2992779 · DOI
  16. [17]Jin G. Sun J. Kim S.T. Feng J. Wang Z. Tao S. Chen Z. Purcell L. Smith S. Isaacs W.B. Genome-Wide Association Study Identifies a New Locus JMJD1C at 10q21 That May Influence Serum Androgen Levels in Men Hum. Mol. Genet. 2012 21 5222 5228 10.1093/hmg/dds361 22936694 PMC3607470 · DOI · Paper page
  17. [18]Svartberg J. Schirmer H. Wilsgaard T. Mathiesen E.B. Njølstad I. Løchen M.L. Jorde R. Single-Nucleotide Polymorphism, Rs1799941 in the Sex Hormone-Binding Globulin (SHBG) Gene, Related to Both Serum Testosterone and SHBG Levels and the Risk of Myocardial Infarction, Type 2 Diabetes, Cancer and Mortality in Men: The Tromsø Study Andrology 2014 2 212 218 10.1111/j.2047-2927.2013.00174.x 24327369 · DOI · Paper page
  18. [19]Moffat S.D. Zondrman A.B. Metter E.J. Kawas C. Blackman M.R. Harman S.M. Resnick S.N. Free Testosterone and Risk of Alzheimer’s Disease in Older Men Neurology 2004 62 188 193 10.1212/WNL.62.2.188 14745052 · DOI
  19. [20]Hogervorst E. Bandelow S. Combrinck M. Smith A.D. Low Free Testosterone Is an Independent Risk Factor for Alzheimer’s Disease Exp. Gerontol. 2004 39 1633 1639 10.1016/j.exger.2004.06.019 15582279 · DOI
  20. [21]Gururani K. Jose J. George P.V. Testosterone as a Marker of Coronary Artery Disease Severity in Middle Aged Males Indian Heart J. 2016 68 S16 S20 10.1016/j.ihj.2016.07.002 28038719 PMC5198878 · DOI
  21. [22]Vermeulen A. Verdonck L. Kaufman J.M. A Critical Evaluation of Simple Methods for the Estimation of Free Testosterone in Serum J. Clin. Endocrinol. Metab. 1999 84 3666 3672 10.1210/jcem.84.10.6079 10523012 · DOI · Paper page
  22. [23]Morales A. Bebb R.A. Manjoo P. Assimakopoulos P. Axler J. Collier C. Elliott S. Goldenberg L. Gottesman I. Grober E.D. Diagnosis and Management of Testosterone Deficiency Syndrome in Men: Clinical Practice Guideline CMAJ 2015 187 1369 1377 10.1503/cmaj.150033 26504097 PMC4674408 · DOI
  23. [27]Li J.-Y. Li X.-Y. Li M. Zhang G.-K. Ma F.-L. Liu Z.-M. Zhang N.-Y. Meng P. Decline of Serum Levels of Free Testosterone in Aging Healthy Chinese Men Aging Male 2005 8 3 4 10.1080/13685530500356010 16390747 · DOI
  24. [28]Yavuz B.B. Ozkayar N. Halil M. Cankurtaran M. Ulger Z. Tezcan E. Gurlek A. Ariogul S. Free Testosterone Levels and Implications on Clinical Outcomes in Elderly Men Aging Clin. Exp. Res. 2008 20 201 206 10.1007/BF03324771 18594186 · DOI
  25. [29]Yeap B.B. Are Declining Testosterone Levels a Major Risk Factor for Ill-Health in Aging Men? Int. J. Impot. Res. 2009 21 24 10.1038/ijir.2008.60 19037223 · DOI
  26. [32]Pye S.R. Phil M. Silman A.J. Finn J.D. Sc B. Neill T.W.O. Bartfai G. Casanueva F.F. Ph D. Forti G. Identification of Late-Onset Hypogonadism in Middle-Aged and Elderly Men N. Engl. J. Med. 2010 363 123 135 20554979
  27. [33]Ramasamy R. Golan R. Wilken N. Scovell J.M. Lipshultz L.I. Association of Free Testosterone with Hypogonadal Symptoms in Men with Near-Normal Total Testosterone Levels HHS Public Access Urology 2015 86 287 290 10.1016/j.urology.2015.05.007 26199166 PMC4549166 · DOI

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Authors
Castellano-Castillo, D., Royo, J. L., Martínez-Escribano, A., Sánchez-Alcoholado, L., Molina-Vega, M., Queipo-Ortuño, M. I., Ruiz-Galdon, M., J. Álvarez-Millán, J., Cabezas-Sanchez, P., Reyes-Engel, A., Tinahones, F. J., Cardona, F., & Fernandez-Garcia, J. C.
Affiliations
  • Unidad de Gestión Clínica de Endocrinología y Nutrición del Hospital Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, 29010 Málaga, Spain
  • Departamento de Especialidades Quirúrgicas, Bioquímica e Inmunología, Universidad de Málaga, 29010 Málaga, Spain
  • Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición, CIBERobn, 28029 Madrid, Spain
  • Consulting Químico Sanitario SL (CQS Lab), 28521 Madrid, Spain
  • Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition (ES)
Corresponding author
  • Tinahones, Francisco J.
  • Cardona, Fernando
ORCID
Venue
Journal of Clinical Medicine
Publisher
MDPI AG
Published
2019-07-31
Volume
8
Issue
8
Pages
1136
ISSN
2077-0383 (ISSN-L)
DOI
10.3390/jcm8081136
PMC
PMC6722847
OpenAlex
W2965175113
Cited by
8
References
6
Citations by year
2025: 2 · 2023: 1 · 2022: 3 · 2021: 2
FWCI
1.01
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Clinical Medicine (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RISalud Institutional Health Repository of Andalucía (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Consejeria de Salud, Junta de Andalucia and co-funded by Fondo Europeo de Desarrollo Regional- FEDER (SAS PI-0173-2013)
  • Formación del Profesorado Universitario (FPU) Program, co-funded by Fondo Europeo de Desarrollo Regional- FEDER (FPU13/04211)
  • “Rio Hortega” Program, co-funded by Fondo Europeo de Desarrollo Regional- FEDER (CM18/0120)
  • Servicio Andaluz de Salud, co-funded by Fondo Europeo de Desarrollo Regional- FEDER (B-0003-2017)
  • Nicolas Monardes Program, from Consejería de Salud, co-funded by the Fondo Europeo de Desarrollo Regional - FEDER (C-0032-2016, C-0030-2018)
  • “Miguel Servet Type II” program, co-funded by the Fondo Europeo de Desarrollo Regional - FEDER (CPI13/00003)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
  • Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
  • Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Keywords
sex hormone-binding globulin, genetic polymorphism, free testosterone, hypogonadism, obesity, young men, non-diabetic obesity, total testosterone

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