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Effect Modification of LHCGR Gene Variant (rs2293275) on Clinico-Biochemical Profile, and Levels of Luteinizing Hormone in Polycystic Ovary Syndrome Patients

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Abstract

 Polycystic ovary syndrome (PCOS) is a common multifaceted endocrine disorder among reproductive-aged women. Deranged luteinizing hormone levels and associated downstream signaling cascade mediated by its receptor luteinizing hormone chorionic gonadotropin receptor (LHCGR) are pivotal in the etiopathogenesis of PCOS. Genetic variations in the LHCGR have been associated with PCOS risk. However, the results are mixed and inconclusive. We evaluated the association of the LHCGR rs2293275 polymorphic variant with PCOS risk and its association with clinico-biochemical features of PCOS. 120 confirmed PCOS cases and an equal number of age-matched controls were subjected to clinical, biochemical, and hormonal investigations. Genotyping for rs2293275 was performed using polymerase chain reaction-restriction fragment length polymorphism. Logistic regression models were used to calculate odds ratios (ORs) at 95% confidence intervals (95% CIs). In the current study, PCOS cases reported a lower number of menstrual cycles per year than respective controls. A significantly higher BMI, Ferriman Galway score, levels of serum testosterone, insulin, TSH, FSH, and fasting glucose were observed in cases than in controls (p < 0.01). Compared to GG carriers, we observed a higher risk of developing PCOS in the subjects who harbored GA (OR 10.4, p < 0.0001) or AA (OR 7.73, p = 0.02) genotype. The risk persisted in the dominant model (GA + AA) as well (OR 10.29, p = 0.01). On stratification, a higher risk of developing PCOS was observed in variant genotype carriers who had a family history of either type two diabetes mellitus (OR 117; p < 0.0001) or hirsutism (OR 79; p < 0.0001). We also found significantly elevated levels of serum LH levels in the subject harboring GA and AA genotypes when compared to GG carriers. In the present study, we report a significant association of the LHCGR rs2293275 variant with the PCOS risk.

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Acknowledgements

The authors thank all the participants for volunteering in the study. The authors also thank the Multi-disciplinary Research Unit, SKIMS, Srinagar funded by the Department of Health Research, Govt of India, for providing necessary research facilities for carrying out this study.

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The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

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Authors and Affiliations

  1. Department of Life Sciences, Jaipur National University, Jaipur, India

    Mudassir Jan Makhdoomi, Rabiya Rashid & Saurabh singh

  2. Departments of Endocrinology, Sheri Kashmir Institute of Medical Sciences, Srinagar, India

    Mudassir Jan Makhdoomi, Rabiya Rashid, Aafia Rashid & Mohd Ashraf Ganie

  3. Multidisciplinary Research Unit, Sheri Kashmir Institute of Medical Sciences, Srinagar, India

    Idrees A. Shah & Mohd Ashraf Ganie

  4. Departments of Immunology and Molecular Medicine, Sheri Kashmir Institute of Medical Sciences, Srinagar, India

    Zaffar Amin Shah

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Contributions

MAG conceived the study; MJM, MAG, ZAS, and SS designed the study. MJM and AR collected the data, and MJM and RR performed experiments. IAS, MJM, and MAG analyzed and interpreted the data. MJM, IAS, and MAG wrote the first draft of the manuscript. All the authors reviewed and approved the final draft of the manuscript.

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Correspondence to Mohd Ashraf Ganie.

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Ethical Approval

This study was approved by the institutional ethics committee of SKIMS (SKIMS-IEC) under protocol number RP 55/19.

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Makhdoomi, M.J., Shah, I.A., Rashid, R. et al. Effect Modification of LHCGR Gene Variant (rs2293275) on Clinico-Biochemical Profile, and Levels of Luteinizing Hormone in Polycystic Ovary Syndrome Patients. Biochem Genet 61, 1418–1432 (2023). https://doi.org/10.1007/s10528-022-10327-z

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