Journal of Reproduction & Infertility

Journal of Reproduction & Infertility

An Association Study between INSR/NsiI (rs2059806) and INSR/PmlI (rs1799817) SNPs in Women with Polycystic Ovary Syndrome from West Azerbaijan Province, Iran

Authors
1 Food and Beverages Safety Research Center, Urmia University of Medical Sciences, Urmia, Iran; Cellular and Molecular Research Center, Urmia University of Medical Sciences, Urmia, Iran
2 Food and Beverages Safety Research Center, Urmia University of Medical Sciences, Urmia, Iran
3 Reproductive Health Research Center, Department of Obstetrics and Gynecology, Urmia University of Medical Sciences, Urmia, Iran
4 Cellular and Molecular Research Center, Urmia University of Medical Sciences, Urmia, Iran
Abstract
Background: It has been demonstrated that insulin signaling pathway related genes have important roles in polycystic ovary syndrome (PCOS) risk. The goal of present investigation was to assess the potential association between INSR/NsiI (rs2059806) and INSR/PmlI (rs1799817) SNPs and PCOS. Methods: 50 women with PCOS and 47 normal controls entered the study. NsiI and PmlI SNPs in the INSR gene were determined by RFLP-PCR. Results: INSR/NsiI (rs2059806) SNP GG, GA, AA, G and A genotypic and allelic frequencies were 45(90%), 5(10%), 0(0%), 95(95%) and 5(5%) in cases and 41(87.2%), 6(12.8%), 0(0%), 88(93.6%) and 6(6.38%) in controls, respectively. INSR/PmlI (rs1799817) SNPs resulted in three genotypes of CC, CT, and TT with C and T alleles. The frequencies of PmlI (rs1799817) SNPs in the INSR gene were 37(37%) and 63(63%) in cases, also 39(41.49%) and 55 (58.51%) in controls regarding T and C alleles. The frequencies of PmlI (rs1799817) SNPs in the INSR gene were 4(8%), 29(58%), and 17(34%) in cases, also 5(10.64%), 29(61.7%), and 13(27.66%) in controls regarding TT, TC, and CC genotypes, respectively. Conclusion: The present study as the first investigation of its own kind in Iranian Azeri Turkish women, reported no association between NsiI (rs2059806) and PmlI (rs1799817) SNPs in the INSR gene and PCOS risk.
Keywords

  1. Ranjzad F, Mahmoudi T, Irani Shemirani A, Mahban A, Nikzamir A, Vahedi M, et al. A common variant in the adiponectin gene and polycystic ovary syndrome risk. Mol Biol Rep. 2012;39(3):2313-9.
  2. Mukherjee S, Shaikh N, Khavale S, Shinde G, Meherji P, Shah N, et al. Genetic variation in exon 17 of INSR is associated with insulin resistance and hyperandrogenemia among lean Indian women with polycystic ovary syndrome. Eur J Endocrinol. 2009;160(5):855-62.
  3. Talbot JA, Bicknell EJ, Rajkhowa M, Krook A, O'Rahilly S, Clayton RN. Molecular scanning of the insulin receptor gene in women with polycystic ovarian syndrome. J Clin Endocrinol Metab. 1996;81(5):1979-83.
  4. Chen ZJ, Shi YH, Zhao YR, Li Y, Tang R, Zhao LX, et al. [Correlation between single nucleotide polymorphism of insulin receptor gene with polycystic ovary syndrome]. Zhonghua Fu Chan Ke Za Zhi. 2004;39(9):582-5. Chinese.
  5. Chen ZJ, Zhao H, He L, Shi Y, Qin Y, Shi Y, et al. Genome-wide association study identifies susceptibility loci for polycystic ovary syndrome on chromosome 2p16.3, 2p21 and 9q33.3. Nat Genet. 2011;43(1):55-9.
  6. Lee EJ, Yoo KJ, Kim SJ, Lee SH, Cha KY, Baek KH. Single nucleotide polymorphism in exon 17 of the insulin receptor gene is not associated with polycystic ovary syndrome in a Korean population. Fertil Steril. 2006;86(2):380-4.
  7. Jin L, Zhu XM, Luo Q, Qian Y, Jin F, Huang HF. A novel SNP at exon 17 of INSR is associated with decreased insulin sensitivity in Chinese women with PCOS. Mol Hum Reprod. 2006;12(3):151-5.
  8. Siegel S, Futterweit W, Davies TF, Concepcion ES, Greenberg DA, Villanueva R, et al. A C/T single nucleotide polymorphism at the tyrosine kinase domain of the insulin receptor gene is associated with polycystic ovary syndrome. Fertil Steril. 2002;78(6):1240-3.
  9. Xu X, Zhao H, Shi Y, You L, Bian Y, Zhao Y, et al. Family association study between INSR gene polymorphisms and PCOS in Han Chinese. Reprod Biol Endocrinol. 2011;9:76.
  10. Ranjzad F, Mahban A, Shemirani AI, Mahmoudi T, Vahedi M, Nikzamir A, et al. Influence of gene variants related to calcium homeostasis on biochemical parameters of women with polycystic ovary syndrome. J Assist Reprod Genet. 2011;28(3):225-32.
  11. Taylor SI, Kadowaki T, Kadowaki H, Accili D, Cama A, McKeon C. Mutations in insulin-receptor gene in insulin-resistant patients. Diabetes Care. 1990;13(3):257-79.
  12. Dunaif A, Scott D, Finegood D, Quintana B, Whitcomb R. The insulin-sensitizing agent troglitazone improves metabolic and reproductive abnormalities in the polycystic ovary syndrome. J Clin Endocrinol Metab. 1996;81(9):3299-306.
  13. Ott J, Wattar L, Kurz C, Seemann R, Huber JC, Mayerhofer K, et al. Parameters for calcium metabolism in women with polycystic ovary syndrome who undergo clomiphene citrate stimulation: a prospective cohort study. Eur J Endocrinol. 2012;166(5):897-902.
  14. Farmakiotis D, Katsikis I, Panidis D. Calcium homeostasis and anovulatory infertility. Hum Reprod. 2007;22(12):3264.
  15. 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;81(1):19-25.
  16. Zawadski JK, Dunaif A. Diagnostic criteria for polycystic ovary syndrome: towards a rational approach. Boston: Blackwell Scientific Publications; 1992. 377 p.
  17. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16(3):1215.
  18. Sagodi L, Kiss-Toth E, Barkai L. [Role of genetic and environmental factors in the development of polycystic ovary syndrome]. Orv Hetil. 2013;154(17):650-7. Hungarian.
  19. Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev. 1997;18(6):774-800.
  20. Stepto NK, Cassar S, Joham AE, Hutchison SK, Harrison CL, Goldstein RF, et al. Women with polycystic ovary syndrome have intrinsic insulin resistance on euglycaemic-hyperinsulaemic clamp. Hum Reprod. 2013;28(3):777-84.
  21. Barber TM, Franks S. The link between polycystic ovary syndrome and both Type 1 and Type 2 diabetes mellitus: what do we know today? Womens Health (Lond Engl). 2012;8(2):147-54.
  22. Nestler JE. Role of hyperinsulinemia in the pathogenesis of the polycystic ovary syndrome, and its clinical implications. Semin Reprod Endocrinol. 1997;15(2):111-22.
  23. Carmina E. Ovarian and adrenal hyperandrogenism. Ann N Y Acad Sci. 2006;1092:130-7.
  24. Markopoulos MC, Rizos D, Valsamakis G, Deligeoroglou E, Grigoriou O, Chrousos GP, et al. Hyperandrogenism in women with polycystic ovary syndrome persists after menopause. J Clin Endocrinol Metab. 2011;96(3):623-31.
  25. Sirmans SM, Weidman-Evans E, Everton V, Thompson D. Polycystic ovary syndrome and chronic inflammation: pharmacotherapeutic implications. Ann Pharmacother. 2012;46(3):403-18.
  26. Schmidt J, Landin-Wilhelmsen K, Brannstrom M, Dahlgren E. Cardiovascular disease and risk factors in PCOS women of postmenopausal age: a 21-year controlled follow-up study. J Clin Endocrinol Metab. 2011;96(12):3794-803.
  27. Wild S, Pierpoint T, McKeigue P, Jacobs H. Cardiovascular disease in women with polycystic ovary syndrome at long-term follow-up: a retrospective cohort study. Clin Endocrinol (Oxf). 2000;52(5):595-600.
  28. Bentley-Lewis R, Seely E, Dunaif A. Ovarian hypertension: polycystic ovary syndrome. Endocrinol Metab Clin North Am. 2011;40(2):433-49.
  29. Usadi RS, Legro RS. Reproductive impact of polycystic ovary syndrome. Curr Opin Endocrinol Diabetes Obes. 2012;19(6):505-11.
  30. Bhattacharya SM. Insulin resistance and overweight-obese women with polycystic ovary syndrome. Gynecol Endocrinol. 2010;26(5):344-7.
  31. Ramezani Tehrani F, Daneshpour M, Hashemi S, Zarkesh M, Azizi F. Relationship between polymorphism of insulin receptor gene, and adiponectin gene with PCOS. Iran J Reprod Med. 2013;11(3):185-94.
  32. Unsal T, Konac E, Yesilkaya E, Yilmaz A, Bideci A, Ilke Onen H, et al. Genetic polymorphisms of FSHR, CYP17, CYP1A1, CAPN10, INSR, SERPINE1 genes in adolescent girls with polycystic ovary syndrome. J Assist Reprod Genet. 2009;26(4):205-16.
  33. Urbanek M, Sam S, Legro RS, Dunaif A. Identification of a polycystic ovary syndrome susceptibility variant in fibrillin-3 and association with a metabolic phenotype. J Clin Endocrinol Metab. 2007;92(11):4191-8.