STUDY OF CYTOCHROME P450 C 17 ALPHA (CYP17A1) GENE POLYMORPHISM IN PATIENTS WITH POLY CYSTIC OVARIAN SYNDROME

Kazhal Muhammad Sulaiman

doi:10.46903/gjms/22.03.1727

STUDY OF CYTOCHROME P450 C 17 ALPHA (CYP17A1) GENE POLYMORPHISM IN PATIENTS WITH POLY CYSTIC OVARIAN SYNDROME

Kazhal Muhammad Sulaiman

Abstract

Background: Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine disorder characterized by hormonal imbalances and metabolic issues. This study aimed to explore the association between CYP17A1 polymorphism and PCOS severity.

Materials & Methods: This analytical case-control study was conducted at Salahaddin University from January 2023 to December 2023. Convenience sampling was used to include participants in the study. This study included 150 patients with PCOS and 50 controls, classified according to PCOS severity using Rotterdam criteria. Clinical assessments, hormonal profiling, and genetic analyses were also performed. CYP17A1 polymorphisms were identified using Restriction Fragment Length Polymorphism (RFLP), Sanger sequencing, and High-Resolution Melt (HRM) analysis.

Results: CYP17A1 polymorphisms varied significantly across the groups (p <0.001), with 4 (8%) in controls, 11 (22%) with mild PCOS, 8 (16%) with moderate PCOS, and 21 (42%) with severe PCOS. Regression analysis revealed significant associations between testosterone level (coefficient =4.8765, p <0.001), Ferriman-Gallwey score (coefficient =0.2345, p <0.001), LH/FSH ratio (coefficient =2.789, p <0.001), and PCOS severity. Polymorphisms were associated with higher testosterone levels (coefficient = 0.2156, P <0.001) and an increased risk of PCOS (odds ratio =1.9238, P =0.005).

Conclusion: The findings of this study revealed a strong correlation between CYP17A1 gene polymorphisms and the development and severity of PCOS. The findings of this study indicate the involvement of CYP17A1 in PCOS etiology, specifically in androgen excess and gonadal dysfunction.

Keywords

Humans; Poly Cystic Ovarian syndrome; gene polymorphism; genotyping; hormonal assessment; Body Mass Index.

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References

Li Y, Fang Y, Wang H, Zhang H. Balancing Act: Exploring the Gut Microbiota-Brown Adipose Tissue Axis in PCOS Pathogenesis and Therapeutic Frontiers. Front Biosci (Landmark Ed). 2024;29(6): 208. https://doi.org/10.31083/j.fbl2906208

Petersen LK, Brixi G, Li J, Hu J, Wang Z, Han X, et al. Understanding and Predicting Polycystic Ovary Syndrome through Shared Genetic Architecture with Testosterone, SHBG, and Inflammatory Markers. medRxiv. 2024: 2023.10.17.23297115. https://doi.org/10.1101/2023.10.17.23297115

Doulgeraki T, Papageorgopoulou M, Iliodromiti S. The genetic background of female reproductive disorders: a systematic review. Current Opinion in Obstetrics & Gynecology. 2023;35(5): 426-33. https://doi.org/10.1097/gco.0000000000000896

Zhu J, Eliasen AU, Aris IM, Stinson SE, Holm JC, Hansen T, et al. Pediatric Features of Genetic Predisposition to Polycystic Ovary Syndrome. The Journal of clinical endocrinology and metabolism. 2024;109(2): 380-8. https://doi.org/10.1210/clinem/dgad533

Meczekalski B, Niwczyk O, Kostrzak A, Maciejewska-Jeske M, Bala G, Szeliga A. PCOS in Adolescents-Ongoing Riddles in Diagnosis and Treatment. J Clin Med. 2023;12(3): 1221. https://doi.org/10.3390/jcm12031221

Moosa A, Ghani M, O’Neill HC. Genetic associations with polycystic ovary syndrome: the role of the mitochondrial genome; a systematic review and meta-analysis. J Clin Pathol. 2022;75(12): 815-24. https://doi.org/10.1136/jcp-2021-208028

Rosenfield RL. Current concepts of polycystic ovary syndrome pathogenesis. Current opinion in pediatrics. 2020;32(5): 698-706. https://doi.org/10.1097/mop.0000000000000945

Heidarzadehpilehrood R, Pirhoushiaran M, Abdollahzadeh R, Binti Osman M, Sakinah M, Nordin N, et al. A Review on CYP11A1, CYP17A1, and CYP19A1 Polymorphism Studies: Candidate Susceptibility Genes for Polycystic Ovary Syndrome (PCOS) and Infertility. Genes. 2022;13(2): 302. https://doi.org/10.3390/genes13020302

Ихтиярова Г, Музаффарова М. The role of determinant genes of steroid hormones dysfunction regulators (cyp17a1-rs743572, cyp19a1-rs247015) in the development of pcos in women with infertility. Международный журнал научной педиатрии. 2022;1(7): 05-11. https://doi.org/10.56121/2181-2926-2022-7-05-11

Guo X, Zhong Y, Liu Y, Wu R, Huang L, Huang C, et al. Oocyte-derived Factor GDF9 Suppresses Expression of StAR and CYP17A1 in Human Theca Cells. Res Sq. 2021: 1-15.

Rezgoun ML, El Khour D, Bendaoud H, Chellat D. CYP17A1 (rs74357) polymorphism and polycystic ovary syndrome risk: a systemic review and meta-analysis. Acta bio-medica : Atenei Parmensis. 2023;94(4): e2023167. https://doi.org/10.23750/abm.v94i4.14229

Xing C, Zhao H, Zhang J, He B. The Association of CYP17A1, CYP19A1, and SHBG Gene Polymorphisms in Polycystic Ovary Syndrome Susceptibility: A Systematic Review and Meta-Analysis. Front Physiol. 2022;13: 741285. https://doi.org/10.3389/fphys.2022.741285

Kaur R, Kaur T, Kaur A. Genetic association study from North India to analyze association of CYP19A1 and CYP17A1 with polycystic ovary syndrome. J Assist Reprod Genet. 2018;35(6): 1123-9. https://doi.org/10.1007/s10815-018-1162-0

Park JM, Lee EJ, Ramakrishna S, Cha DH, Baek KH. Association study for single nucleotide polymorphisms in the CYP17A1 gene and polycystic ovary syndrome. Int J Mol Med. 2008;22(2): 249-54

Fang Y, Liu L, Yang Y, Zhang B, Xie S. Causal Association Between BMI and Polycystic Ovarian Syndrome: Bidirectional 2-Sample Mendelian Randomization Study. J Clin Endocrinol Metab. 2024. https://doi.org/10.1210/clinem/dgae446

DOI: https://doi.org/10.46903/gjms/22.03.1727