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
Open accessAbstract
Low testosterone levels are associated with metabolic and cardiovascular disease risk factor, and have been shown to predict type 2 diabetes mellitus (T2DM), myocardial infarction (MI) and all-cause mortality. It is not known if these associations are causal or not. Recently, it has been shown that the serum testosterone levels are associated with single-nucleotide polymorphisms (SNPs), and we therefore studied the associations between one of these SNPs, rs1799941 on the Sex Hormone-Binding Globulin (SHBG) gene, and MI, T2DM, cancer and death. DNA was prepared from men who participated in the fourth survey of the Tromsø Study in 1994-1995 and who were registered with the endpoints MI, T2DM, cancer or death and a randomly selected control group. For mortality, the observation time was set from 1994, and for the other endpoints from birth. The endpoint data were completed up to 2010-2013. Genetic analyses were successfully performed in 5309 men, of whom 1454 were registered with MI, 638 with T2DM, 1534 with cancer and in 2226 who had died. Men with the minor homozygote genotype had significantly higher levels of total testosterone (14.7%) and SHBG (24.7%) compared with men with the major homozygote genotype, whereas free testosterone levels did not differ significantly between the genotypes. The SNP rs1799941 was not significantly associated with MI, T2DM, cancer or mortality. Thus, our result does not support a causal relationship between total testosterone and SHBG and MI, T2DM, cancer or mortality, suggesting that low testosterone more likely is a marker of poor health.
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For the rare homozygous AA genotype of rs1799941, an increase in both serum SHBG and T was observed as opposed to the reference genotype.
“Second, for the rare homozygous AA genotype of rs1799941, an increase in both serum SHBG and T was observed as opposed to the reference genotype [66, 69, 72, 73].”
From Role of sex hormone-binding globulin in the free hormone hypothesis and the relevance of free testosterone in androgen physiology (2022) · cites this paper as [73]
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Bhasin, S., Cunningham, G. R., Hayes, F. J., Matsumoto, A. M., Snyder, P. J., Swerdloff, R. S., & Montori, V. M. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-2354 · Cited by 1,954 · see citing works
Rosner, W., Auchus, R. J., Azziz, R., Sluss, P. M., & Raff, H. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-1864 · Cited by 1,176 · see citing works
Khaw, K.-T., Dowsett, M., Folkerd, E., Bingham, S., Wareham, N., Luben, R., Welch, A., & Day, N. (2007) · Circulation · doi:10.1161/circulationaha.107.719005 · Cited by 743 · see citing works
Endogenous Testosterone and Mortality in Men: A Systematic Review and Meta-Analysis
Araujo, A. B., Dixon, J. M., Suarez, E. A., Murad, M. H., Guey, L. T., & Wittert, G. A. (2011) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2011-1137 · Cited by 671 · see citing works
Oh, J.-Y., Barrett-Connor, E., Wedick, N. M., & Wingard, D. L. (2002) · Diabetes Care · doi:10.2337/diacare.25.1.55 · Cited by 594 · see citing works
Effect of Testosterone Treatment on Body Composition and Muscle Strength in Men Over 65 Years of Age
Snyder, P. J. (1999) · Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.84.8.2647 · Cited by 531 · see citing works
Svartberg, J., Midtby, M., Bonaa, K., Sundsfjord, J., Joakimsen, R., & Jorde, R. (2003) · European Journal of Endocrinology · doi:10.1530/eje.0.1490145 · Cited by 257 · see citing works
Self-citationGenetic determinants of serum testosterone concentrations in men
Ohlsson, C., Wallaschofski, H., Lunetta, K. L., Stolk, L., Perry, J. R. B., Koster, A., Petersen, A.-K., Eriksson, J., Lehtimäki, T., Huhtaniemi, I. T., et al. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1002313 · Cited by 224 · see citing works
Perry, J. R. B., Weedon, M. N., Langenberg, C., Jackson, A. U., Lyssenko, V., Sparsø, T., Thorleifsson, G., Grallert, H., Ferrucci, L., Maggio, M., et al. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddp522 · Cited by 217 · see citing works
Predictive accuracy and sources of variability in calculated free testosterone estimates
Sartorius, G., Ly, L. P., Sikaris, K., McLachlan, R., & Handelsman, D. J. (2009) · Annals of Clinical Biochemistry: International Journal of Laboratory Medicine · doi:10.1258/acb.2008.008171 · Cited by 175 · see citing works
Svartberg, J., Agledahl, I., Figenschau, Y., Sildnes, T., Waterloo, K., & Jorde, R. (2008) · International Journal of Impotence Research · doi:10.1038/ijir.2008.19 · Cited by 160 · see citing works
Self-citationVikan, T., Schirmer, H., Njølstad, I., & Svartberg, J. (2010) · European Journal of Endocrinology · doi:10.1530/eje-09-0943 · Cited by 151 · cited 2× · see citing works
“…levels tends to predict the development of metabolic syndrome and type 2 diabetes mellitus (T2DM) (Oh et al., 2002; Laaksonen et al., 2004; Vikan et al., 2010) and have been associated with both all-cause mortality and cardiovascular disease (CVD) mortality (Vikan et al., 2009a; Araujo…”
BackgroundSelf-citationTestosterone therapy decreases subcutaneous fat and adiponectin in aging men
Frederiksen, L., Højlund, K., Hougaard, D. M., Mosbech, T. H., Larsen, R., Flyvbjerg, A., Frystyk, J., Brixen, K., & Andersen, M. (2012) · European Journal of Endocrinology · doi:10.1530/eje-11-0565 · Cited by 93 · see citing works
Basu, R., Man, C. D., Campioni, M., Basu, A., Nair, K. S., Jensen, M. D., Khosla, S., Klee, G., Toffolo, G., Cobelli, C., et al. (2007) · Diabetes Care · doi:10.2337/dc07-0359 · Cited by 91 · see citing works
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Research works printed but not linked: 1
- Ding EL, Song Y, Malik VS & Liu S. (2006) Sex differences of endogenous sex hormones and risk of type 2 diabetes: a systematic review and meta-analysis. JAMA 295, 1288-1299.
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Narinx, N., David, K., Walravens, J., Vermeersch, P., Claessens, F., Fiers, T., Lapauw, B., Antonio, L., & Vanderschueren, D. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-022-04562-1 · Cited by 96 · see citing works
Ageing male (part I): Pathophysiology and diagnosis of functional hypogonadism
Huhtaniemi, I. T., & Wu, F. C. W. (2022) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1016/j.beem.2022.101622 · Cited by 31 · see citing works
- Authors
- Svartberg, J., Schirmer, H., Wilsgaard, T., Mathiesen, E. B., Njølstad, I., Løchen, M.-L., & Jorde, R.
- Affiliations
- University Hospital of North Norway (NO)
- UiT The Arctic University of Norway (NO)
- Corresponding author
- Svartberg, J.
- Venue
- Andrology
- Publisher
- Wiley
- Published
- 2013-12-10
- Volume
- 2
- Issue
- 2
- Pages
- 212-218
- ISSN
- 2047-2919 (ISSN-L)
- OpenAlex
- W2167239412
- Cited by
- 32
- References
- 14
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 2 · 2022: 4 · 2019: 8 · 2018: 4 · 2017: 1 · 2016: 1 · 2015: 6 · 2014: 1
- FWCI
- 2.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Andrology (publishedVersion)
- PubMed (publishedVersion)
- Research Bank (Australian Catholic University) (submittedVersion)
- Funders
- Society for Endocrinology
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Keywords
- sex hormone-binding globulin, SHBG gene, single nucleotide polymorphisms, total testosterone, free testosterone, androgen deficiency, myocardial infarction, type 2 diabetes, cancer, all-cause mortality, men, genetic association, causal inference, biomarkers
- MeSH terms
- Aged, Diabetes Mellitus, Type 2, Genotype, Humans, Life Style, Longitudinal Studies, Male, Middle Aged, Myocardial Infarction, Neoplasms, Surveys and Questionnaires, Sex Hormone-Binding Globulin, Testosterone, Epidemiologic Studies, Polymorphism, Single Nucleotide
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