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Susceptibility loci identified in Han Chinese influence genetic predisposition of PCOS in Indian women

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Abstract

Background

Polycystic ovary syndrome (PCOS) is a multifactorial disorder characterized by a broad spectrum of reproductive and metabolic perturbations, necessitating early timely diagnosis and management. PCOS is a multigenic disorder and ample evidence from family based, candidate gene and genome-wide association studies (GWAS) has implicated genetic factors in development and progression of PCOS. The first GWASs in Han Chinese population revealed prominent gene loci to be strong contenders in the etiopathogenesis of PCOS. However, different ethnic and geographical settings impact the genetic association pattern of PCOS.

Methods and results

In the current case-control replication study, we have genotyped previously identified polymorphisms viz. rs2479106 and rs10818854 of DENND1A and rs13405728 of LHCGR, rs4385527 and rs3802457 of c9orf3, rs705702 of RAB5B and rs1894116 of YAP1 in control (N = 247) and PCOS (N = 504) women by Sanger sequencing, and their association with PCOS susceptibility and its related traits was investigated. We found significant association of rs4385527 of c9orf3 and rs1894116 of YAP1 with decreased and increased PCOS susceptibility respectively in non-hyperandrogenic women. Trend towards association was also noted for rs2479106 of DENND1A and rs705702 of RAB5B. Additionally, polymorphisms also showed association with metabolic and androgen related traits in both controls and hyper- and non-hyperandrogenic women with PCOS.

Conclusions

Thus, this study shows that some, but not all polymorphisms previously identified in Han Chinese women, could contribute to the genetic pathophysiology of PCOS in Indian women, accentuating essentiality of conducting replication studies to elucidate the genetic predisposition profile of PCOS.

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Acknowledgements

The authors are thankful to all the study participants and the staff of the multidisciplinary PCOS clinic at ICMR-NIRRCH. This work is partially supported by Department of Science and Technology (CRG/2019/001457), National Institute for Research in Reproductive and Child Health (RA/1500/02-2023) and Indian Council of Medical Research (ICMR), New Delhi, India. The authors are deeply appreciative for all the technical support received from Ms. Gayatri Shinde, Ms Dhanashree Gaikwad and Ms. Mahalakshmi Bhat.

Funding

This work is partially supported by Department of Science and Technology (CRG/2019/001457), NIRRCH (NIRRCH/RA/1500/02-2023) and Indian Council of Medical Research (ICMR), New Delhi, India.

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Authors and Affiliations

  1. Department of Molecular Endocrinology, ICMR-National Institute for Research in Reproductive and Child Health, J.M. Street, Parel, Parel, Mumbai, 400012, India

    Roshan Dadachanji, Sushma Khavale, Nanda Joshi & Srabani Mukherjee

  2. Department of Clinical Research, ICMR-National Institute for Research in Reproductive and Child Health, Parel, Mumbai, 400012, India

    Anushree Patil

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  1. Roshan Dadachanji
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Contributions

RD, SK and NJ performed all investigations and experiments and curated data, RD performed formal analysis and interpretation and wrote the manuscript, AP was responsible for recruitment and characterization of study participants, SM was responsible for conceptualization, study design, funding acquisition, project administration, providing critical revisions and approving the final manuscript.

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Correspondence to Srabani Mukherjee.

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This study was approved by the human ethics committee of ICMR-National Institute for Research in Reproductive and Child Health (295/2016).

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Dadachanji, R., Khavale, S., Joshi, N. et al. Susceptibility loci identified in Han Chinese influence genetic predisposition of PCOS in Indian women. Mol Biol Rep 51, 160 (2024). https://doi.org/10.1007/s11033-023-09004-0

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