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Peroxisome proliferator activated receptor gamma gene variants influence susceptibility and insulin related traits in Indian women with polycystic ovary syndrome

  • Genetics
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

Peroxisome proliferator activated receptor gamma (PPARγ), a transcription factor involved in glucose and lipid metabolism is one of the candidate genes associated with polycystic ovary syndrome (PCOS). We investigated individual and combined associations of Pro12Ala and His447His polymorphisms of PPARγ with PCOS susceptibility and its related traits (hyperinsulinemia, hyperandrogenemia and lipid parameters) in Indian women.

Method

Genotyping of PPARγ polymorphisms in this case–control study was performed in PCOS (n = 450) and age-matched controls (n = 300) by direct sequencing. Clinical, anthropometric, hormonal and metabolic parameters were estimated in 275 women with PCOS and 169 controls. Chi-square test was used to compare the categorical data while regression analysis was used to evaluate association of genotypes with PCOS as well as its related phenotypes.

Results

The frequencies of CC and CG + GG genotypes of Pro12Ala (χ 2 = 15.3, p < 0.0001) and CC and CT + TT genotypes of His447His (χ 2 = 12.7, p = 0.0004) polymorphisms were significantly different between PCOS and controls. Logistic regression analysis revealed a significant association of PCOS with Pro12Ala but not the His447His polymorphism. Carriers of variant genotypes at both PPARγ loci showed significantly reduced 2 h glucose levels while carriers of variant His447His genotype showed lower fasting insulin and HOMA-IR levels in PCOS women.

Conclusions

Pro12Ala polymorphism of PPARγ showed significant association with decreased PCOS susceptibility. Both polymorphisms influenced insulin related traits (2 h glucose, fasting insulin and HOMA-IR) and improved glucose metabolism in these women. This is the first report to establish that variations in PPARγ gene influence the insulin resistance pathophysiology in Indian women with PCOS.

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Funding

This work was partially funded by Department of Science and Technology, Govt. of India (Project No: SR/SO/HS-60/2005). We would like to acknowledge the financial assistance provided by Department of Science and Technology (DST) and Indian Council of Medical Research (ICMR), India to NS for carrying her doctoral studies.

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Authors and Affiliations

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

    Nuzhat Shaikh & Srabani Mukherjee

  2. National Institute of Biomedical Genomics, Kalyani, West-Bengal, 741251, India

    Ankur Mukherjee

  3. Seth G. S. Medical College and KEM Hospital, Mumbai, 400012, India

    Nalini Shah

  4. Department of Infertility, National Institute for Research in Reproductive Health, Mumbai, 400012, India

    Pervin Meherji

Authors
  1. Nuzhat Shaikh
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  2. Ankur Mukherjee
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  3. Nalini Shah
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  4. Pervin Meherji
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  5. Srabani Mukherjee
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Corresponding author

Correspondence to Srabani Mukherjee.

Additional information

Capsule Pro12Ala but not His447His polymorphism of PPARγ shows significant association with PCOS susceptibility. However both polymorphisms influence insulin related traits in Indian women with PCOS.

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Shaikh, N., Mukherjee, A., Shah, N. et al. Peroxisome proliferator activated receptor gamma gene variants influence susceptibility and insulin related traits in Indian women with polycystic ovary syndrome. J Assist Reprod Genet 30, 913–921 (2013). https://doi.org/10.1007/s10815-013-0025-y

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  • DOI: https://doi.org/10.1007/s10815-013-0025-y

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