Indian Journal of Medical Biochemistry

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VOLUME 25 , ISSUE 3 ( September-December, 2021 ) > List of Articles

ORIGINAL RESEARCH ARTICLE

Interesting Phenomenon of Primer-induced Mutagenesis Seen in Subjects with Respect to PPARγPro12Ala Polymorphism in Polycystic Ovary Syndrome

Monika Garg, Anju Jain, Binita Goswami, Manju Puri

Keywords : Insulin resistance, Polycystic ovary syndrome, PPARγPro12Ala polymorphism

Citation Information : Garg M, Jain A, Goswami B, Puri M. Interesting Phenomenon of Primer-induced Mutagenesis Seen in Subjects with Respect to PPARγPro12Ala Polymorphism in Polycystic Ovary Syndrome. Indian J Med Biochem 2021; 25 (3):110-112.

DOI: 10.5005/jp-journals-10054-0182

License: CC BY-NC 4.0

Published Online: 11-03-2022

Copyright Statement:  Copyright © 2021; The Author(s).


Abstract

Introduction: Polycystic ovary syndrome (PCOS), the commonest cause of endocrinal disorder in women of reproductive age, has a very wide spectrum of presentations. Insulin resistance is most frequently associated with PCOS. PPARγPro12Ala polymorphism; by reducing insulin resistance in PCOS subjects has emerged as one of the promising modalities of treatment of this syndrome. Aim and objective: To explain the phenomenon of primer-induced mutagenesis with the help of PPARγPro12Ala polymorphism in subjects with PCOS. Materials and methods: A hospital-based case-control study was carried out in 50 diagnosed cases of PCOS (15–45 years of age); according to revised Rotterdam Criteria along with 50 age and BMI-matched apparently healthy controls. PPARγPro12Ala polymorphism was detected through DNA extraction from whole blood followed by PCR and restriction fragment length polymorphism (RFLP) using restriction enzyme BstU1 Fast Digest. When the C → G substitution at nucleotide 34 is present (missense mutation CCA to GCA), the mutagenic downstream primer introduces a BstU1 restriction site (CG || CG). The expected products after digestion with BstU1 are 270 bp for normal homozygotes, 227 and 43 bp for Pro12Ala homozygotes, and 270, 227, and 43 bp for heterozygotes. Statistical analysis was performed using SPSS version 16 through an independent sample t-test for intergroup comparison of means and Pearson's correlation coefficient for correlation analysis. Categorical data analysis for polymorphism was carried out using the Chi-square test. Results and conclusion: There was no significant difference in the genotypic distribution of C/G genotypes between cases and controls. Cases with CG genotype were associated with higher insulin sensitivity when compared with CC genotype though it was not statistically significant.


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  1. Ramanand SJ, Ghongane BB, Ramanand JB, et al. Clinical characteristics of polycystic ovary syndrome in Indian women. Indian J Endocrinol Metab 2013;17(1):138–145. DOI: 10.4103/2230-8210.107858.
  2. Wehr E, Trummer O, Giuliani A, et al. Vitamin D-associated polymorphisms are related to insulin resistance and vitamin D deficiency in polycystic ovary syndrome. Eur J Endocrinol 2011;164(5):741–749. DOI: 10.1530/EJE-11-0134.
  3. Lakkakula BV, Thangavelu M, Godla UR. 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 2013;30(7):883–895. DOI: 10.1007/s10815-013-0030-1.
  4. Marshall JC, Dunaif A. All women with PCOS should be treated for insulin resistance. Fertil Steril 2012;97(1):18–22. DOI: 10.1016/j.fertnstert.2011.11.036.
  5. Kintscher U, Law RE. PPARγ-mediated insulin sensitization: the importance of fat versus muscle. Am J Physiol Endocrinol Metab 2005;288(2):E287–E291. DOI: 10.1152/ajpendo.00440.2004.
  6. Molavi B, Rassouli N, Bagwe S, et al. A review of thiazolidinediones and metformin in the treatment of type 2 diabetes with focus on cardiovascular complications. Vasc Health Risk Manag 2007;3(6):967–973.
  7. Botta M, Audano M, Sahebkar A, et al. PPAR agonists and metabolic syndrome: an established role? Int J Mol Sci 2018. 1–21.
  8. Eldor R, DeFronzo RA, Abdul-Ghani M. In vivo actions of peroxisome proliferator–activated receptors glycemic control, insulin sensitivity, and insulin secretion. Diabetes Care 2013;36(Suppl 2):S162–S174. DOI: 10.2337/dcS13-2003.
  9. Chandra V, Huang P, Hamuro Y, et al. Structure of the intact PPAR gamma–RXR–nuclear receptor complex on DNA. Nature 2008;456(7220):350–356. DOI: 10.1038/nature07413.
  10. Wang L, Waltenberger B, Pferschy-Wenzig EM, et al. Natural product agonists of peroxisome proliferator-activated receptor gamma (PPARγ): a review. Biochem Pharmacol 2014;92(1):73–89. DOI: 10.1016/j.bcp.2014.07.018.
  11. Stumvoll M, Häring H. Perspectives in diabetes. The peroxisome proliferator – activated receptor – γ2 Pro12Ala polymorphism. Diabetes 2002;51(8):2341–2347. DOI: 10.2337/diabetes.51.8.2341.
  12. Zeng ZR, Leung WK, Zhou SZ, et al. Peroxisome proliferator activated receptor-gamma Pro12Ala polymorphism, helicobacter pylori infection and non-cardia gastric carcinoma in Chinese. Aliment Pharmacol Ther 2006;23(2):289–294. DOI: 10.1111/j.1365-2036.2006.02739.x.
  13. Schoonjans K, Staels B, Auwerx J. Role of the peroxisome proliferator-activated receptor (PPAR) in mediating the effects of fibrates and fatty acids on gene expression. J Lipid Res 1996;37(5):907–925. DOI: 10.1016/S0022-2275(20)42003-6.
  14. Saremi L, Lotfipanah S, Mohammadi M, et al. The Pro12Ala polymorphism in the PPARγ2 gene is not associated with an increased risk of NAFLD in Iranian patients with type 2 diabetes mellitus. Cell Mol Biol Lett 2019;24(1):12. DOI: 10.1186/s11658-019-0138-0.
  15. Yen C-J, Beamer BA, Negri C, et al. Molecular scanning of the human peroxisome proliferator activated receptor γ (hPPAR-γ) gene in diabetic caucasians: identification of a Pro12Ala PPAR γ2 missense mutation. Biochem Biophys Res Commun 1997;241(2):270–274. DOI: 10.1006/bbrc.1997.7798.
  16. Yang J, Gong H, Liu W, et al. The association of Pro12Ala polymorphism in the peroxisome proliferator-activated receptor-gamma2 gene with the metabolic characteristics in Chinese women with polycystic ovary syndrome. Int J Clin Exp Pathol 2013;6(9):1894–1902.
  17. Bhatt SP, Misra A, Sharma M, et al. Ala/Ala genotype of Pro12Ala polymorphism in the peroxisome proliferator-activated receptor-γ2 gene is associated with obesity and insulin resistance in Asian Indians. Diabetes Technol Ther 2012;14(9):828–834. DOI: 10.1089/dia.2011.0277.
  18. Jacob R, Ramachandran C, Jude C. Peroxisome proliferator activated receptor gamma polymorphism Pro12Ala in polycystic ovary syndrome (PCOS) of South Indian population. Asian Pac J Reprod 2016;5(3):210–213. DOI: 10.1016/j.apjr.2016.04.002.
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