Effect of SHBG Polymorphism on the Levels of Bioavailable Testosterone and Lipid Metabolism in Older Men of the Kazakh Population


  • Merkhat Akkaliyev Department of Surgical Disciplines, Semey Medical University, Semey, Kazakhstan https://orcid.org/0000-0003-3122-7411
  • Nurlan Aukenov Department of Health and Human Resources, Ministry of Health of the Republic of Kazakhstan
  • Meruyert Massabayeva Department of Surgical Disciplines, Semey Medical University, Semey, Kazakhstan https://orcid.org/0000-0001-8240-361X
  • Bakytbek Apsalikov Department of Surgical Disciplines, Semey Medical University, Semey, Kazakhstan https://orcid.org/0000-0001-6983-9224
  • Saule Rakhyzhanova Department of Surgical Disciplines, Semey Medical University, Semey, Kazakhstan
  • Muratkhan Kuderbaev Department of Surgical Disciplines, Semey Medical University, Semey, Kazakhstan
  • Nariman Sadykov Department of Surgery, Pavlodar Branch of the Semey Medical University, Pavlodar, Kazakhstan




SHBG, Bioavailable testosterone, Hypogonadism, Lipid metabolism disorders in men


This study is aimed at investigating the effect of SHBG (rs727428; rs10822184) and LPL (rs754493647) single nucleotide polymorphisms on the concentration of the bioavailable fraction of testosterone in older men.

Materials and methods To study gene mutations, 417 residents of the East Kazakhstan region of Kazakh nationality were examined. The main group included 135 men with signs of hypogonadism (AMS 37-49), and the control group consisted of 282 healthy men (AMS 17-26) of the corresponding age (p = 0.5). Single nucleotide polymorphisms rs 727428 [C / T]; rs10822184 [T / C]; rs754493647 [T / C], was determined by the TaqMan method.

Results Analysis of the rs727428 polymorphism has revealed that the TT allele (rs727428) has a lower level of albumin (p = 0.03), bioavailable testosterone (p = 0.04), and free testosterone (p = 0.6) than in carriers of the CC and CT genotypes. Also, it has shown a decrease in total testosterone (p = 0.001) and an increase in SHBG levels (p = 0.07) in men with the TT genotype of the rs727428 gene polymorphism. The rs10822184 polymorphism demonstrated an increase in triglyceride and LDL levels in TT genotype (p ≤ 0.04), in comparison with CC and CT genotypes.

Conclusion It has been proven that rs727428 (p = 0.001) is associated with testosterone levels and therefore can determine the concentration of bioavailable testosterone. Decreased levels of bioavailable testosterone are a sign of male hypogonadism. This study confirms the effect of rs10822184 on LDL (p = 0.01) and triglyceride (p = 0.04) levels, but its association with androgen levels has not been proven. Our results may be of interest for understanding the etiology of early development of hypogonadism and lipid metabolism disorders in men. To confirm the conclusions, a more detailed study with a large sample of men from the Kazakh population may be required.


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Nassar GN, Leslie SW. Physiology, Testosterone. Treasure Island: StatPearls; 2019.

Lunenfeld B, Mskhalaya G, Zitzmann M, Arver S, Kalinchenko S, Tishova Y, et al Recommendations on the diagnosis, treatment and monitoring of hypogonadism in men. Aging Male. 2015;18(1):5- 15. https://doi.org/10.3109/13685538.2015.100404 PMid:25657080 DOI: https://doi.org/10.3109/13685538.2015.1004049

Beck T, Shorter T, Brookes AJ. GWAS Central: A comprehensive resource for the discovery and comparison of genotype and phenotype data from genome-wide association studies. Nucleic Acids Res. 2020;48(D1):D933-40. https://doi.org/10.1093/nar/gkz895 DOI: https://doi.org/10.1093/nar/gkz895

Li C, Ford ES, Li B, Giles WH, Liu S. Association of testosterone and sex hormone-binding globulin with metabolic syndrome and insulin resistance in men. Diabetes Care. 2010;33(7):1618-24. https://doi.org/10.2337/dc09-1788 PMid:20368409 DOI: https://doi.org/10.2337/dc09-1788

Rosner W, Hryb DJ, Kahn SM, Nakhla AM, Romas NA. Interactions of sex hormone-binding globulin with target cells. Mol Cell Endocrinol. 2010;316(1):79-85. https://doi.org/10.1016/j.mce.2009.08.009 PMid:19698759 DOI: https://doi.org/10.1016/j.mce.2009.08.009

Hammond GL. Diverse roles for sex hormone-binding globulin in reproduction. Biol Reprod. 2011;85(3):431-41. https://doi.org/10.1095/biolreprod.111.092593 DOI: https://doi.org/10.1095/biolreprod.111.092593

Li H, Pham T, McWhinney BC, Ungerer JP, Pretorius CJ, Richard DJ, et al. Sex hormone binding globulin modifies testosterone action and metabolism in prostate cancer cells. Int J Endocrinol. 2016;2016:6437585. https://doi.org/10.1155/2016/6437585 PMid:27990161 DOI: https://doi.org/10.1155/2016/6437585

Tint AN, Hoermann R, Wong H, Ekinci EI, Macisaac RJ, Jerums G, et al. Association of sex hormone-binding globulin and free testosterone with mortality in men with Type 2. Eur J Endocrinol. 2016;174(1):59-68. https://doi./org/10.1530/EJE-15-0672 PMid:26483395 DOI: https://doi.org/10.1530/EJE-15-0672

Grossmann M. Hypogonadism and male obesity: Focus on unresolved questions. Clin Endocrinol (Oxf). 2018;89(1):11-21. https://doi.org/10.1111/cen.13723 PMid:29683196 DOI: https://doi.org/10.1111/cen.13723

Fernandez CJ, Chacko EC, Pappachan JM. Male obesity-related secondary hypogonadism pathophysiology, clinical implications and management. Eur Endocrinol. 2019;15(2):83-90. https://doi.org/10.17925/EE.2019.15.2.83 PMid:31616498 DOI: https://doi.org/10.17925/EE.2019.15.2.83

Kersten S. Physiological regulation of lipoprotein lipase. Biochim Biophys Acta. 2014;1841(7):919-33. https://doi.org/10.1016/j.bbalip.2014.03.013 PMid:24721265 DOI: https://doi.org/10.1016/j.bbalip.2014.03.013

Andrade MC Jr. Lipoprotein lipase: A general review. Insights Enzyme Res. 2018;2(1):1-13. https://doi.org/10.21767/2573-4466.100013 DOI: https://doi.org/10.21767/2573-4466.100013

Tao S, Wang Z, Feng J, Hsu FC, Jin G, Kim ST, et al. A genome-wide search for loci interacting with known prostate cancer risk-associated genetic variants. Carcinogenesis. 2012;33(3):598-603. https://doi.org/10.1093/carcin/bgr316 PMid:22219177 DOI: https://doi.org/10.1093/carcin/bgr316

Hammond GL. Access of reproductive steroids to target tissues. Obstet Gynecol Clin North Am. 2002;29(3):411-23. https://doi. org/10.1016/s0889-8545(02)00008-6 PMid:12353665 DOI: https://doi.org/10.1016/S0889-8545(02)00008-6

Keevil BG, Adaway J. Assessment of free testosterone concentration. J Steroid Biochem Mol Biol. 2019;190:207-11. https://doi.org/10.1016/j.jsbmb.2019.04.008 PMid:30970279 DOI: https://doi.org/10.1016/j.jsbmb.2019.04.008

Simó R, Sáez-López C, Barbosa-Desongles A, Hernández C, Selva DM. Novel insights in SHBG regulation and clinical implications. Trends Endocrinol Metab. 2015;26(7):376-83. https://doi.org/10.1016/j.tem.2015.05.001 PMid:26044465 DOI: https://doi.org/10.1016/j.tem.2015.05.001

Morgentaler A, Traish A, Hackett G, Jones TH, Ramasamy R. Diagnosis and treatment of testosterone deficiency: Updated recommendations from the Lisbon 2018 international consultation for sexual medicine. Sex Med Rev. 2019;7(4):636- 49. https://doi.org/10.1016/j.sxmr.2019.06.003 PMid:31351915 DOI: https://doi.org/10.1016/j.sxmr.2019.06.003

García-Cruz E, Alcaraz A. Testosterone deficiency syndrome: Diagnosis and treatment. Actas Urol Esp (Engl Ed). 2020;44(5):294-300. https://doi.org/10.1016/j.acuro.2019.10.009 PMid:32423612 DOI: https://doi.org/10.1016/j.acuroe.2019.10.008

Jin G, Sun J, Kim ST, Feng J, Wang Z, Tao S, et al. Genome-wide association study identifies a new locus JMJD1C at 10q21 that may influence serum androgen levels in men. Hum Mol Genet. 2012;21(23):5222-8. https://doi.org/10.1093/hmg/dds361 PMid:22936694 DOI: https://doi.org/10.1093/hmg/dds361

Ohlsson C, Wallaschofski H, Lunetta KL, Stolk L, Perry JR, Koster A, et al. Genetic determinants of serum testosterone concentrations in men. PLoS Genet. 2011;7(10):e1002313. https://doi.org/10.1371/journal.pgen.1002313 PMid:21998597 DOI: https://doi.org/10.1371/journal.pgen.1002313

Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR, Baltimore Longitudinal Study of Aging longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore longitudinal study of aging. J Clin Endocrinol Metab. 2001;86(2):724-31. https://doi.org/10.1210/jcem.86.2.7219 PMid:11158037 DOI: https://doi.org/10.1210/jcem.86.2.7219

Daka B, Rosen T, Jansson PA, Råstam L, Larsson CA, Lindblad U. Inverse association between serum insulin and sex hormone-binding globulin in a population survey in Sweden. Endocr Connect. 2012;2(1):18-22. https://doi.org/10.1530/EC-12-0057 PMid:23781314 DOI: https://doi.org/10.1530/EC-12-0057

Peter A, Kantartzis K, Machann J, Schick F, Staiger H, Machicao F, et al. Relationships of circulating sex hormone-binding globulin with metabolic traits in humans. Diabetes. 2010;59(12):3167-73. https://doi.org/10.2337/db10-0179 PMid:20841609 DOI: https://doi.org/10.2337/db10-0179

Wallace IR, McKinley MC, Bell PM, Hunte SJ. Sex hormone binding globulin and insulin resistance. Clin Endocrinol (Oxf). 2013;78(3):321-9. https://doi.org/10.1111/cen.12086 PMid:23121642 DOI: https://doi.org/10.1111/cen.12086

Sun K, Wang C, Lao G, Lin D, Huang C, Li N, et al. Lipid accumulation product and late-onset hypogonadism in middle-aged and elderly men: Results from a cross-sectional study in China. BMJ Open. 2020;10(2):e033991. https://doi.org/10.1136/bmjopen-2019-033991 PMid:32047018 DOI: https://doi.org/10.1136/bmjopen-2019-033991

Wu FC, Tajar A, Beynon JM, Pye SR, Silman AJ, Finn JD, et al. Identification of late-onset hypogonadism in middle-aged and elderly men. N Engl J Med. 2010;363(2):123-35. https://doi.org/10.1056/NEJMoa0911101 PMid:20554979 DOI: https://doi.org/10.1056/NEJMoa0911101




How to Cite

Akkaliyev M, Aukenov N, Massabayeva M, Apsalikov B, Rakhyzhanova S, Kuderbaev M, Sadykov N. Effect of SHBG Polymorphism on the Levels of Bioavailable Testosterone and Lipid Metabolism in Older Men of the Kazakh Population. Open Access Maced J Med Sci [Internet]. 2022 Jul. 22 [cited 2024 Apr. 20];10(A):1315-20. Available from: https://oamjms.eu/index.php/mjms/article/view/8145

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