Molecular Basis of Insulin Signaling Pathway in Pathogenesis of Polycystic Ovary Syndrome

Polycystic ovary syndrome is a heterogeneous disorder affecting millions of women and most common cause of anovulatory infertility. Insulin resistance plays key role in its pathogenesis & reproductive abnormalities. Post binding defects in insulin receptor signaling is now considered major molec...

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Bibliographic Details
Published inIndian journal of clinical biochemistry Vol. 34; no. S1; p. S80
Main Authors Rani, A, Bagra, P, Choudhari, O, Suri, J
Format Journal Article
LanguageEnglish
Published Springer 24.05.2022
Subjects
Cellular signal transduction
Disease susceptibility
Genetic research
Insulin
Insulin resistance
Single nucleotide polymorphisms
Stein-Leventhal syndrome
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ISSN0970-1915

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Summary:Polycystic ovary syndrome is a heterogeneous disorder affecting millions of women and most common cause of anovulatory infertility. Insulin resistance plays key role in its pathogenesis & reproductive abnormalities. Post binding defects in insulin receptor signaling is now considered major molecular basis of insulin resistance in PCOS. Single nucleotide polymorphism in tyrosine kinase domain of insulin receptor gene has been shown to be significantly associated with development of PCOS. Insulin receptor substrate proteins are also critical for insulin mediated signal transduction. Besides, genetic polymorphism is distinct in specific population, ethnicity, geographical region due to exposure to different environmental factors. Keeping in view present study was conducted to explore genes involved in insulin signaling and risk of PCOS in north Indian females. A case control study was conducted in department of biochemistry & department of obstetrics & gynecology at VMMC & Safdarjung hospital, New Delhi. 100 cases of PCOS & 100 controls were included in this study. The DNA extraction was done using KRISHGEN DNA kit & genotyping was done by PCR-RFLP. Subjects with CT genotypes had 2.47 times higher risk of developing PCOS as compared to CC genotype (OR=2.47, CI=1.3-4.6, p-value= 0.006). Subjects with TT genotype have 5.6 times higher risk of developing PCOS as compared to CC genotype (OR=5.6, 0=2.41-13, 3-value [less than or equal to] 2.223). Both CT & TT genotype of insulin receptor (INSR) gene SNP (rs 1799817 C->T) is associated with hyperinsulinemia, insulin resistance & increased susceptibility to PCOS. Insulin receptor gene may be considered as a candidate gene for predisposition to PCOS & its metabolic dysfunction. Both CT & TT genotype of INSR gene SNPs (rs3799837) constitutes a significant proportion of general population. Hence, it could be screened & therapeutic approach can be designed accordingly to lessen co-morbidities associated with PCOS.
ISSN:0970-1915