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Association of TCF7L2 Gene Variant (rs12255372) with Polycystic Ovary Syndrome and its Effect Modification of the Disease Phenotype

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Abstract

Polycystic ovary syndrome (PCOS) and type-2 diabetes mellitus (T2DM) share common genetic features. Transcription factor 7-like-2 (TCF7L2) is consistently studied T2DM susceptibility locus. However, limited studies on TCF7L2 have failed to demonstrate any link with the PCOS risk. Therefore, we investigated the association of TCF7L2 polymorphic variant (rs12255372) with the PCOS risk. We recruited 120 PCOS cases, diagnosed as per Rotterdam 2003 criteria, and an equal number of age-matched controls. Besides a detailed clinical assessment, subjects underwent biochemical and hormonal profiling. Genoty** for rs12255372 was done by PCR–RFLP. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95%CIs) of genotype–phenotype correlations. The PCOS cases reported fewer menstrual cycles per year and exhibited signs of hyperandrogenism. The heterozygous genotype of rs12255372 was strongly associated with the PCOS risk (OR = 2.00; 95%CI: 1.07–3.76). Unlike controls, only 3 cases harbored TT genotype, and the PCOS risk persisted in the dominant model (GT + TT) as well. Moreover, we found a synergistic effect modification by the variant genotype in the subjects who had family histories of T2DM, hirsutism, or menstrual irregularities. We report a significant association of the TCF7L2 polymorphic variant rs12255372 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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Authors and Affiliations

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

    Rabiya Rashid, Mudassir Jan Makhdoomi & Meena Godha

  2. Multidisciplinary Research Unit, Department of Clinical Research, SKIMS, Srinagar, India

    Rabiya Rashid, Idrees A. Shah & Mohd Ashraf Ganie

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

    Mudassir Jan Makhdoomi, Aafia Rashid & Mohd Ashraf Ganie

  4. Centre for Research and Development, University of Kashmir, Srinagar, India

    Bashir A. Ganai

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  1. Rabiya Rashid
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Contributions

MA Ganie conceived the study; MA Ganie, BA Ganai and M Godha designed the study. R Rashid and A Rashid collected the data, R Rashid and M J Makhdoomi performed experiments. IA Shah, R Rashid and MA Ganie analyzed and interpreted the data. R Rashid, IA Shah, and MA Ganie 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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Rashid, R., Shah, I.A., Makhdoomi, M.J. et al. Association of TCF7L2 Gene Variant (rs12255372) with Polycystic Ovary Syndrome and its Effect Modification of the Disease Phenotype. Ind J Clin Biochem 39, 373–379 (2024). https://doi.org/10.1007/s12291-023-01115-6

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  • DOI: https://doi.org/10.1007/s12291-023-01115-6

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