The Relation of the SHBG Gene Polymorphism (rs1799941) with PCOS in a Group of Iraqi Women

Authors

  • Rusul Hisham Master's Student, Department of Biology, College of Science, University of Tikrit, IRAQ.
  • Dr. Adel Fawzy Shehab Professor, Department of Biology, College of Science, University of Tikrit, IRAQ.
  • Hadeel Abdel-Hadi Omair Assistant Professor, Department of Biology, College of Science, University of Tikrit, IRAQ.

DOI:

https://doi.org/10.55544/jrasb.1.4.16

Keywords:

PCOS (Polycystic Ovary Syndrome), SHBG (Six Hormone Binging Globulin)

Abstract

Polycystic Ovary Syndrome (PCOS) is the most common and complex endocrine disorder that affects women of childbearing age. However, the causes of PCOS are still unknown, however, there is strong evidence supporting the role of genetics in causing it, because PCOS has a strong familial predisposition. More than one gene contributes to the heterogeneous phenotype and clinical and biochemical presentation. Patients with PCOS may complain of irregular menstruation, unwanted hair growth in multiple areas of the body, acne and scalp hair loss, unexplained weight gain, and infertility. This study explores the polymorphism of the SHBG gene locus (rs1799941) in Iraqi women with PCOS that may cause the onset of this disease. Genomic DNA was extracted from blood samples of women with and without PCOS. The SHBG gene was amplified by Tetra_ARMS PCR technology, after which the PCR product was migrated onto the agarose jells at a concentration of 2%. Three genotypes appeared, the homozygous (normal) homozygous GG which is represented by (404 + 270 bp) genotype, the heterozygous (GA) which is represented by (404 + 270 + 210) bp and the homozygous mutant AA genotype. (Which is represented by the bundle (404 + 210 bp). Among the 70 women with PCOS included in the molecular study, (4) of them were carriers of the normal homozygous genotype GG, (44) of them were carriers of the heterozygous genotype GA and (22) were carrying the mutated genotype AA. In the current study, the (OR) value of the mixed GA genotype appeared (12.833) and this indicates that the mixed genotype is a risk factor for the disease, while the (OR) value of the AA mutant genotype was (9.250), and this indicates that the mutant genotype is Homozygous is a risk factor for the disease. The frequency of the A allele was higher in the infection group compared to the control group, and this indicates that the A allele is responsible for the disease association. These results indicated that the locus SHBG gene polymorphism (rs1799941) is associated with PCOS in Iraqi women.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

References

Wolf, W.M.; Wattick, R.A.; Kinkade, O.N.; Olfert, M.D. Geographical Prevalence of Polycystic Ovary Syndrome as Determined by Region and Race/Ethnicity. Int. J. Environ. Res. Public Health 2018, 15, 25892.

Bozdag, G.; Mumusoglu, S.; Zengin, D.; Karabulut, E.; Yildiz, B.O. The prevalence and phenotypic features of polycystic ovary syndrome: A systematic review and meta-analysis. Hum. Reprod. 2016, 31, 2841–2855.

Anagnostis, P.; Tarlatzis, B.C.; Kauffman, R.P. Polycystic ovarian syndrome (PCOS): Long-term metabolic consequences. Metabolism 2018, 86, 33–43.

Khan, M.J.; Ullah, A.; Basit, S. Genetic Basis of Polycystic Ovary Syndrome (PCOS): Current Perspectives. Appl. Clin. Genet. 2019, 12, 249–260.

Menke MN , Strauss JF 2007 Genetic approaches to polycystic ovarian syndrome. Curr Opin Obstet Gynecol 19:355–359.

Cousin P , Calemard-Michel L , Lejeune H , Raverot G , Yessaad N , Emptoz-Bonneton A , Morel Y , Pugeat M 2004 Influence of SHBG gene pentanucleotide TAAAA repeat and D327N polymorphism on serum sex hormone-binding globulin concentration in hirsute women. J Clin Endocrinol Metab 89:917–924.

Hammond, G. L ., Underhill, D. A ., Smith, C.L ., Goping, I. S ., Harley, M. J., Musto, N. A., Cheng, C. Y ., Bardin, C .W . (1987). The cDNA-deduced primary structure of human sex hormone-binding globulin and location of its steroid-binding domain. FEBS Lett 215:100-4.

Qu, X and Donnelly, R . (2020). Sex Hormone-Binding Globulin (SHBG) as an Early Biomarker and Therapeutic Target in Polycystic Ovary Syndrome. Int. J. Mol. Sci. 21, 8191. P 1-17.

Bhatnager, R., Senwal, A., Nanda, S., & Dang, A. S. (2019). Association of rs6259 polymorphism with SHBG levels and Poly Cystic Ovary Syndrome in Indian population: a case control study. Molecular biology reports, 46(2), 2131-2138.

Hammond GL 1990 Molecular properties of corticosteroid binding globulin and the sex-steroid binding proteins. Endocr Rev 11:65–79.

Deswal, R., Yadav, A., & Dang, A. S. (2018). Sex hormone binding globulin-an important biomarker for predicting PCOS risk: A systematic review and meta-analysis. Systems biology in reproductive medicine, 64(1), 12-24.

Xita N , Tsatsoulis A , Chatzikyriakidou A , Georgiou I 2003 Association of the (TAAAA)n repeat polymorphism in the sex hormone-binding globulin (SHBG) gene with polycystic ovary syndrome and relation to SHBG serum levels. J Clin Endocrinol Metab 88:5976–598

Danilowicz, K., Bruno, O.D., Mana, D., Serra, H.A., Cross, G. and Rey, J.A. (2014). [Female hyperandrogenemia and nor- mal serum levels of testosterone and sex hormone binding globulin]. Medicina (B. Aires) 74:359-362.

Meriem, G., Nesrine, C., Mounir. A., Zouhair. T. and Monia1, Z.A. (2016). Sex Hormone Binding Globulin as a Predictor of in Vitro Fertilization Outcomes in Polycystic Ovary Syndrome: Our Results. Open Journal of Obstetrics and Gynecology 6 :404–410.

Zhu, J. L., Chen, Z., Feng, W. J., Long, S. L., & Mo, Z. C. (2019). Sex hormone-binding globulin and polycystic ovary syndrome. Clinica chimica acta, 499, 142-148.

Shorakae, S., Ranasinha, S., Abell, S., Lambert, G., Lambert, E., de Courten, B., & Teede, H. (2018). Inter‐related effects of insulin resistance, hyperandrogenism, sympathetic dysfunction and chronic inflammation in PCOS. Clinical endocrinology, 89(5), 628-633.‏

Pasquali, R., Zanotti, L., Fanelli, F., Mezzullo, M., Fazzini, A., Morselli Labate, A. M., ... & Gambineri, A. (2016). Defining hyperandrogenism in women with polycystic ovary syndrome: a challenging perspective. The Journal of Clinical Endocrinology & Metabolism, 101(5), 2013-2022‏.

Dumitrescu, R., Mehedintu, C., Briceag, I., Purcarea, V.L .(2015). The Polycystic Ovary Syndrome: An update on metabolic and hormonal mechanisms. Journal of Medicine and Life. 8(2): 142-145.

Karakas, S. E. (2017). New biomarkers for diagnosis and management of polycystic ovary syndrome. Clinica Chimica Acta, 471, 248-253.

Hammond, G. L ., Underhill, D. A ., Smith, C.L ., Goping, I. S ., Harley, M. J., Musto, N. A., Cheng, C. Y ., Bardin, C .W . (1987). The cDNA-deduced primary structure of human sex hormone-binding globulin and location of its steroid-binding domain. FEBS Lett 215:100-4.

Abu-Hijleh T.M. · Gammoh E. · Al-Busaidi A.S. · Malalla Z.H. · Madan S. · Mahmood N. · Almawi W.Y. (2016). Common Variants in the Sex Hormone-Binding Globulin (SHBG) Gene Influence SHBG Levels in Women with Polycystic Ovary Syndrome .6(8),66-74.

Castellano-Castillo D, Royo JL, Martínez-Escribano A, et al. Effects of SHBG rs1799941 Polymorphism on Free Testosterone Levels and Hypogonadism Risk in Young Non-Diabetic Obese Males. J Clin Med. 2019;8(8):1136. Published 2019 Jul 31. doi:10.3390/jcm8081136.

Riancho, J.A., Valero, C., Zarrabeitia, M.T., García-Unzueta, M.T., Amado, J.A., González-Macías, J.(2008). Genetic polymorphisms are associated with serum levels of sex hormone binding globulin in postmenopausal women. BMC Med Genet. 9:112. Published 2008 Dec 17. doi:10.1186/1471-2350-9-112.

Downloads

Published

2022-10-31

How to Cite

Hisham, R., Shehab, A. F., & Omair, H. A.-H. (2022). The Relation of the SHBG Gene Polymorphism (rs1799941) with PCOS in a Group of Iraqi Women. Journal for Research in Applied Sciences and Biotechnology, 1(4), 124–128. https://doi.org/10.55544/jrasb.1.4.16