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Genetic variants associated with insulin signaling and glucose homeostasis in the pathogenesis of insulin resistance in polycystic ovary syndrome: a systematic review

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Abstract

Background

Polycystic ovary syndrome must be recognized as a serious issue due to its implication on long term health regardless of an individual’s age. PCOS and insulin resistance are interlinked, as approximately 40 % of women with PCOS are insulin resistant. However, the detailed molecular basis for insulin resistance that is coupled with PCOS remains poorly understood.

Objective

To review the published evidence that polymorphisms in genes that are involved in insulin secretion and action are associated with an increased risk of PCOS.

Methods

We reviewed articles published through November 2012 which concerned polymorphisms of genes related to insulin signaling and glucose homeostasis as well as their associations with PCOS. The articles were identified via Medline searches.

Conclusions

No consistent evidence emerged of a strong association between the risk of PCOS and any known gene that is related to insulin signaling and glucose homeostasis. Moreover, recent genome-wide association studies are inconsistent in identifying the associations between PCOS and insulin metabolism genes. Many of the studies reviewed were limited by heterogeneity in the PCOS diagnosis and by not have having a sufficient number of study participants. Further studies are warranted to determine predisposing risk factors which could modify environmental factors and thus reduce the risk of PCOS. Large genome-wide association studies devoted solely to PCOS will be necessary to identify new candidate genes and proteins that are involved in PCOS risk.

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Acknowledgments

Dr. LVKSB and Dr. GUR acknowledge funding from the Department of Biotechnology (DBT), Government of India (Project Ref. No. BT/PR14090/GBD/27/275/2010).

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Correspondence to Bhaskar Venkata Kameswara Subrahmanya Lakkakula.

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Capsule Majority of women with polycystic ovary syndrome are insulin resistant. Polymorphisms of genes related to insulin signaling and glucose homeostasis as well as their associations with PCOS were reviewed. The studies are limited by heterogeneity in the PCOS diagnosis and no strong evidence for association between the risk of PCOS and these gene polymorphisms was found.

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Lakkakula, B.V.K.S., Thangavelu, M. & Godla, U.R. Genetic variants associated with insulin signaling and glucose homeostasis in the pathogenesis of insulin resistance in polycystic ovary syndrome: a systematic review. J Assist Reprod Genet 30, 883–895 (2013). https://doi.org/10.1007/s10815-013-0030-1

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