Covid-19 Research

Original Article

Association of eNOS and STAT6 Gene Polymorphisms with the Susceptibility of Polycystic Ovary Syndrome in South Indian Women

Journal of Biomedical Research & Environmental Sciences article abstract with citation details, DOI, publication dates, subject areas, full text links, and references.

View DOI Submit Manuscript

Article Details

Publication record, authors, dates, abstract, and full text access.

Open Access
Article Type Original Article
Subject Medicine Group
OCLC 9427627243
Manjula Bhanoori*, Veena KV, Swapna Siddamalla, Praveen Guruvaiah, Tumu Venkat Reddy, Suresh Govatati, Mamata Deenadayal and Sisinthy Shivaji
Issue: Volume3-Issue1
Pages: 007-013
Received: 2021-12-28
Accepted: 2022-01-07
Published: 2022-01-08

Abstract

Purpose: Polycystic Ovary Syndrome (PCOS) is a complex multifactorial endocrine metabolic disorder of reproductive-aged women characterized by hyperandrogenism, hirsutism, anovulation, hyperinsulinemia and polycystic ovaries. The main aim of this study was to investigate the association of eNOS and STAT6 gene Single Nucleotide Polymorphisms (SNPs) with the susceptibility of PCOS in South Indian Women.

Research question: What is the association status of eNOS and STAT6 SNPs with PCOS?

Methods: The present genetic association study involves clinically confirmed PCOS patients (n = 105) and non-PCOS controls (n = 110) of the Dravidian linguistic group. Genotyping of +894G/T (Glu298Asp) SNP of eNOS and 2964G/A SNP of STAT6 was performed by Polymerase Chain Reaction (PCR) and sequencing analysis.

Results: There were statistically significant differences in the genotype and allele frequencies of eNOS+894G/T (p = 0.1110) and STAT62964G/A (0.0019) between the cases and controls, according to codominant, dominant and recessive genotype models.

Conclusion: In conclusion, the eNOS and STAT6 gene polymorphisms may constitute an inheritable risk factor for PCOS in South Indian women.

FullText HTML FullText PDF DOI: 10.37871/jbres1393 Crossmark

Certificate of Publication

Certificate of Publication

Copyright

© 2022 Bhanoori M, et al. Distributed under Creative Commons CC-BY 4.0 Creative CommonsAttribution

How to cite this article

Bhanoori M, Veena KV, Siddamalla S, Guruvaiah P, Reddy TV, Govatati S, Deenadayal M, Shivaji S. Association of eNOS and STAT6 Gene Polymorphisms with the Susceptibility of Polycystic Ovary Syndrome in South Indian Women. J Biomed Res Environ Sci. 2022 Jan 08; 3(1): 007-013. doi: 10.37871/jbres1393, Article ID: JBRES1393, Available at: https://www.jelsciences.com/articles/jbres1393.pdf

Subject area(s)

Womens Health and CareGynecology

References

  1. Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab. 2004 Jun;89(6):2745-9. doi: 10.1210/jc.2003-032046. PMID: 15181052.
  2. Siddamalla S, Govatati S, Venu VK, Erram N, Deenadayal M, Shivaji S, Bhanoori M. Association of genetic variations in phosphatase and tensin homolog (PTEN) gene with polycystic ovary syndrome in South Indian women: a case control study. Arch Gynecol Obstet. 2020 Oct;302(4):1033-1040. doi: 10.1007/s00404-020-05658-4. Epub 2020 Jun 24. PMID: 32583210.
  3. Jayasena CN, Franks S. The management of patients with polycystic ovary syndrome. Nat Rev Endocrinol. 2014 Oct;10(10):624-36. doi: 10.1038/nrendo.2014.102. Epub 2014 Jul 15. PMID: 25022814.
  4. McAllister JM, Modi B, Miller BA, Biegler J, Bruggeman R, Legro RS, Strauss JF 3rd. Overexpression of a DENND1A isoform produces a polycystic ovary syndrome theca phenotype. Proc Natl Acad Sci U S A. 2014 Apr 15;111(15):E1519-27. doi: 10.1073/pnas.1400574111. Epub 2014 Mar 31. PMID: 24706793; PMCID: PMC3992676.
  5. Goodarzi MO, Dumesic DA, Chazenbalk G, Azziz R. Polycystic ovary syndrome: etiology, pathogenesis and diagnosis. Nat Rev Endocrinol. 2011 Apr;7(4):219-31. doi: 10.1038/nrendo.2010.217. Epub 2011 Jan 25. PMID: 21263450.
  6. Li L, Baek KH. Molecular genetics of polycystic ovary syndrome: an update. Curr Mol Med. 2015;15(4):331-42. doi: 10.2174/1566524015666150505160140. PMID: 25941819.
  7. Wang F, Pan J, Liu Y et al. Alternative splicing of the androgen receptor in polycystic ovary syndrome. Proc Natl Acad Sci USA. 2015;112(15):4743-4748.
  8. Tumu VR, Govatati S, Guruvaiah P, Deenadayal M, Shivaji S, Bhanoori M. An interleukin-6 gene promoter polymorphism is associated with polycystic ovary syndrome in South Indian women. J Assist Reprod Genet. 2013 Dec;30(12):1541-6. doi: 10.1007/s10815-013-0111-1. Epub 2013 Oct 10. PMID: 24114630; PMCID: PMC3843174.
  9. Guruvaiah P, Govatati S, Reddy TV, Lomada D, Deenadayal M, Shivaji S, Bhanoori M. The VEGF +405 G>C 5' untranslated region polymorphism and risk of PCOS: a study in the South Indian Women. J Assist Reprod Genet. 2014 Oct;31(10):1383-9. doi: 10.1007/s10815-014-0310-4. Epub 2014 Aug 9. PMID: 25106940; PMCID: PMC4171416.
  10. Siddamalla S, Reddy TV, Govatati S, Erram N, Deenadayal M, Shivaji S, Bhanoori M. Vitamin D receptor gene polymorphisms and risk of polycystic ovary syndrome in South Indian women. Gynecol Endocrinol. 2018 Feb;34(2):161-165. doi: 10.1080/09513590.2017.1371128. Epub 2017 Sep 3. PMID: 28868946.
  11. Siddamalla S, Reddy TV, Govatati S, Guruvaiah P, Deenadayal M, Shivaji S, Bhanoori M. Influence of tumour suppressor gene (TP53, BRCA1 and BRCA2) polymorphisms on polycystic ovary syndrome in South Indian women. Eur J Obstet Gynecol Reprod Biol. 2018 Aug;227:13-18. doi: 10.1016/j.ejogrb.2018.05.027. Epub 2018 May 24. PMID: 29860059.
  12. Krishna MB, Joseph A, Thomas PL, Dsilva B, Pillai SM, Laloraya M. Impaired Arginine Metabolism Coupled to a Defective Redox Conduit Contributes to Low Plasma Nitric Oxide in Polycystic Ovary Syndrome. Cell Physiol Biochem. 2017;43(5):1880-1892. doi: 10.1159/000484107. Epub 2017 Oct 20. PMID: 29055959.
  13. Marsden PA, Heng HH, Scherer SW, Stewart RJ, Hall AV, Shi XM, Tsui LC, Schappert KT. Structure and chromosomal localization of the human constitutive endothelial nitric oxide synthase gene. J Biol Chem. 1993 Aug 15;268(23):17478-88. PMID: 7688726.
  14. Sortino MA, Salomone S, Carruba MO, Drago F. Polycystic Ovary Syndrome: Insights into the Therapeutic Approach with Inositols. Front Pharmacol. 2017 Jun 8;8:341. doi: 10.3389/fphar.2017.00341. PMID: 28642705; PMCID: PMC5463048.
  15. Rai H, Parveen F, Kumar S, Kapoor A, Sinha N. Association of endothelial nitric oxide synthase gene polymorphisms with coronary artery disease: an updated meta-analysis and systematic review. PLoS One. 2014 Nov 19;9(11):e113363. doi: 10.1371/journal.pone.0113363. PMID: 25409023; PMCID: PMC4237457.
  16. Kim H, Ku SY, Kim SH, Lee GH, Choi YM, Kim JM, Lee TH, Moon SY. Endothelial nitric oxide synthase gene Glu298Asp polymorphism is associated with advanced stage endometriosis. Hum Reprod. 2009 Oct;24(10):2656-9. doi: 10.1093/humrep/dep212. Epub 2009 Jun 16. PMID: 19531501.
  17. Zhao X, Li Q, Yu F, Lin L, Yin W, Li J, Feng X. Gene polymorphism associated with endothelial nitric oxide synthase (4VNTR, G894T, C786T) and unexplained recurrent spontaneous abortion risk: A meta-analysis. Medicine (Baltimore). 2019 Jan;98(4):e14175. doi: 10.1097/MD.0000000000014175. PMID: 30681586; PMCID: PMC6358376.
  18. Ebejer K, Calleja-Agius J. The role of cytokines in polycystic ovarian syndrome. Gynecol Endocrinol. 2013 Jun;29(6):536-40. doi: 10.3109/09513590.2012.760195. Epub 2013 Feb 1. PMID: 23368758.
  19. Karadeniz M, Erdogan M, Zengi A, Tamsel S, Berdeli A, Saygili F, Yilmaz C. Polymorphism of the interleukin-10 gene in polycystic ovary syndrome. Int J Immunogenet. 2008 Apr;35(2):119-23. doi: 10.1111/j.1744-313X.2007.00746.x. Epub 2008 Jan 24. PMID: 18218037.
  20. Junttila IS. Tuning the Cytokine Responses: An Update on Interleukin (IL)-4 and IL-13 Receptor Complexes. Front Immunol. 2018 Jun 7;9:888. doi: 10.3389/fimmu.2018.00888. PMID: 29930549; PMCID: PMC6001902.
  21. Demicco EG, Harms PW, Patel RM, Smith SC, Ingram D, Torres K, Carskadon SL, Camelo-Piragua S, McHugh JB, Siddiqui J, Palanisamy N, Lucas DR, Lazar AJ, Wang WL. Extensive survey of STAT6 expression in a large series of mesenchymal tumors. Am J Clin Pathol. 2015 May;143(5):672-82. doi: 10.1309/AJCPN25NJTOUNPNF. PMID: 25873501; PMCID: PMC4505928.
  22. Bai Y, Yin K, Su T, Ji F, Zhang S. CTHRC1 in Ovarian Cancer Promotes M2-Like Polarization of Tumor-Associated Macrophages via Regulation of the STAT6 Signaling Pathway. Onco Targets Ther. 2020 Jun 17;13:5743-5753. doi: 10.2147/OTT.S250520. PMID: 32606786; PMCID: PMC7306458.
  23. Li S, Sheng B, Zhao M, Shen Q, Zhu H, Zhu X. The prognostic values of signal transducers activators of transcription family in ovarian cancer. Biosci Rep. 2017 Jul 16;37(4):BSR20170650. doi: 10.1042/BSR20170650. PMID: 28536310; PMCID: PMC5518537.
  24. Ziyab AH, Davies GA, Ewart S, Hopkin JM, Schauberger EM, Wills-Karp M, Holloway JW, Arshad SH, Zhang H, Karmaus W. Interactive effect of STAT6 and IL13 gene polymorphisms on eczema status: results from a longitudinal and a cross-sectional study. BMC Med Genet. 2013 Jul 2;14:67. doi: 10.1186/1471-2350-14-67. PMID: 23815671; PMCID: PMC3700873.
  25. Qian X, Gao Y, Ye X, Lu M. Association of STAT6 variants with asthma risk: a systematic review and meta-analysis. Hum Immunol. 2014 Aug;75(8):847-53. doi: 10.1016/j.humimm.2014.06.007. Epub 2014 Jun 19. PMID: 24952213.
  26. Xia B, Crusius JB, Wu J, Zwiers A, van Bodegraven AA, Peña AS. Signal transducer and activator of transcription 6 gene G2964A polymorphism and inflammatory bowel disease. Clin Exp Immunol. 2003 Mar;131(3):446-50. doi: 10.1046/j.1365-2249.2003.02079.x. PMID: 12605697; PMCID: PMC1808642.
  27. Bhanoori M, Deenadayal M, Kennedy S, Shivaji S. The G2964A 3'-untranslated region polymorphism of the signal transducer and activator of transcription 6 gene is associated with endometriosis in South Indian women. Hum Reprod. 2007 Apr;22(4):1026-30. doi: 10.1093/humrep/del486. Epub 2007 Jan 9. PMID: 17213269.
  28. Shaheen G, Jahan S, Bibi N, Ullah A, Faryal R, Almajwal A, Afsar T, Al-Disi D, Abulmeaty M, Al Khuraif AA, Arshad M, Razak S. Association of endothelial nitric oxide synthase gene variants with preeclampsia. Reprod Health. 2021 Jul 28;18(1):163. doi: 10.1186/s12978-021-01213-9. PMID: 34321043; PMCID: PMC8320179.
  29. Dick BP, McMahan R, Knowles T, Becker L, Gharib SA, Vaisar T, Wietecha T, O'Brien KD, Bornfeldt KE, Chait A, Kim F. Hematopoietic Cell-Expressed Endothelial Nitric Oxide Protects the Liver From Insulin Resistance. Arterioscler Thromb Vasc Biol. 2020 Mar;40(3):670-681. doi: 10.1161/ATVBAHA.119.313648. Epub 2020 Jan 30. PMID: 31996027; PMCID: PMC7047596.
  30. Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. 2004 Jan;81(1):19-25. doi: 10.1016/j.fertnstert.2003.10.004. PMID: 14711538.
  31. Bhanoori M, Kameshwari DB, Zondervan KT, Deenadayal M, Kennedy S, Shivaji S. The endothelial nitric oxide synthase Glu298Asp polymorphism is not a risk factor for endometriosis in south Indian women. Eur J Obstet Gynecol Reprod Biol. 2008 Jul;139(1):53-8. doi: 10.1016/j.ejogrb.2008.01.006. Epub 2008 Mar 7. PMID: 18313829.
  32. Biau DJ, Jolles BM, Porcher R. P value and the theory of hypothesis testing: an explanation for new researchers. Clin Orthop Relat Res. 2010 Mar;468(3):885-92. doi: 10.1007/s11999-009-1164-4. PMID: 19921345; PMCID: PMC2816758.
  33. Khan MJ, Ullah A, Basit S. Genetic Basis of Polycystic Ovary Syndrome (PCOS): Current Perspectives. Appl Clin Genet. 2019 Dec 24;12:249-260. doi: 10.2147/TACG.S200341. PMID: 31920361; PMCID: PMC6935309.
  34. Wu H, Yu K, Yang Z. Associations between TNF-α and interleukin gene polymorphisms with polycystic ovary syndrome risk: a systematic review and meta-analysis. J Assist Reprod Genet. 2015 Apr;32(4):625-34. doi: 10.1007/s10815-015-0449-7. Epub 2015 Feb 18. PMID: 25690158; PMCID: PMC4380887.
  35. Chen H, Zhang Y, Li S, Tao Y, Gao R, Xu W, Yang Y, Cheng K, Wang Y, Qin L. The Association Between Genetically Predicted Systemic Inflammatory Regulators and Polycystic Ovary Syndrome: A Mendelian Randomization Study. Front Endocrinol (Lausanne). 2021 Sep 27;12:731569. doi: 10.3389/fendo.2021.731569. PMID: 34646235; PMCID: PMC8503255.
  36. Benson S, Janssen OE, Hahn S, Tan S, Dietz T, Mann K, Pleger K, Schedlowski M, Arck PC, Elsenbruch S. Obesity, depression, and chronic low-grade inflammation in women with polycystic ovary syndrome. Brain Behav Immun. 2008 Feb;22(2):177-84. doi: 10.1016/j.bbi.2007.07.003. Epub 2007 Aug 22. PMID: 17716857.
  37. Field SL, Dasgupta T, Cummings M, Orsi NM. Cytokines in ovarian folliculogenesis, oocyte maturation and luteinisation. Mol Reprod Dev. 2014 Apr;81(4):284-314. doi: 10.1002/mrd.22285. Epub 2013 Dec 13. PMID: 24273059.
  38. Gallinelli A, Ciaccio I, Giannella L, Salvatori M, Marsella T, Volpe A. Correlations between concentrations of interleukin-12 and interleukin-13 and lymphocyte subsets in the follicular fluid of women with and without polycystic ovary syndrome. Fertil Steril. 2003 Jun;79(6):1365-72. doi: 10.1016/s0015-0282(03)00344-3. PMID: 12798884.
  39. Papacleovoulou G, Critchley HO, Hillier SG, Mason JI. IL1α and IL4 signalling in human ovarian surface epithelial cells. J Endocrinol. 2011 Dec;211(3):273-83. doi: 10.1530/JOE-11-0081. Epub 2011 Sep 8. PMID: 21903865.
  40. Shao Y, Cheng Z, Li X, Chernaya V, Wang H, Yang XF. Immunosuppressive/anti-inflammatory cytokines directly and indirectly inhibit endothelial dysfunction--a novel mechanism for maintaining vascular function. J Hematol Oncol. 2014 Oct 31;7:80. doi: 10.1186/s13045-014-0080-6. PMID: 25387998; PMCID: PMC4236671.
  41. Joshi MS, Mineo C, Shaul PW, Bauer JA. Biochemical consequences of the NOS3 Glu298Asp variation in human endothelium: altered caveolar localization and impaired response to shear. FASEB J. 2007 Sep;21(11):2655-63. doi: 10.1096/fj.06-7088com. Epub 2007 Apr 20. PMID: 17449720; PMCID: PMC7460804.
  42. Gao PS, Heller NM, Walker W, Chen CH, Moller M, Plunkett B, Roberts MH, Schleimer RP, Hopkin JM, Huang SK. Variation in dinucleotide (GT) repeat sequence in the first exon of the STAT6 gene is associated with atopic asthma and differentially regulates the promoter activity in vitro. J Med Genet. 2004 Jul;41(7):535-9. doi: 10.1136/jmg.2003.015842. PMID: 15235025; PMCID: PMC1447608.
Publish with JBRES — Peer-reviewed, multidisciplinary Open Access with rapid review, DOI, and global visibility.
Double-Blind CrossRef DOI Discoverable
Submit Manuscript Membership