Volume 12, Issue 7 (8-2014)                   IJRM 2014, 12(7): 499-0 | Back to browse issues page

XML Persian Abstract Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
Mutib M T, Hamdan F B, Al-Salihi A R. INSR gene variation is associated with decreased insulin sensitivity in Iraqi women with PCOs. IJRM 2014; 12 (7) :499-0
URL: http://ijrm.ir/article-1-562-en.html
INSR gene variation is associated with decreased insulin sensitivity in Iraqi women with PCOs
Manal T Mutib1 , Farqad B Hamdan * 2, Anam R Al-Salihi1
1- The High Institute of Infertility Diagnosis and Assisted Reproductive Technology, Al-Nahrain University, Baghdad, Iraq
2- Department of Physiology, College of Medicine, Al-Nahrain University, Baghdad, Iraq , farqadbhamdan@yahoo.com
Abstract:   (2803 Views)
Background: Polycystic ovarian syndrome (PCOS) is a complex, heterogeneous disorder of uncertain etiology with strong genetic background. Insulin resistance is present in the majority of PCOS cases with linkage and association between single nucleotide polymorphisms of insulin receptor (INSR) gene and PCOS.
Objective: To examine whether the exon 17 of INSR gene contributes to genetic susceptibility to PCOS in Iraqi women and its effects on glucose tolerance test and lipid profile.
Materials and Methods: Sixty-five healthy Iraqi women and eighty-four infertile women with PCOS, divided into two subgroups depending on the BMI were studied. Restriction fragment length polymorphism (RFLP-PCR) analysis was performed to determine the genotypes for the His 1058 C/T polymorphism at the tyrosine kinase domain in the INSR gene. Clinical, anthropometric and biochemical parameters were also estimated.
Results: The C/T polymorphism at His 1058 in exon 17 of INSR was associated with PCOS (obese and non-obese). CC genotype frequency was higher in PCOS patients whereas TT genotype was higher in control women. Those with CC genotype had higher BMI, GTT and lipid profile than those with TT genotype.
Conclusion: An association of C/T polymorphism at His1058 of INSR with PCOS in Iraqi women was observed. Its association with indices of insulin resistance and dyslipidemia were also noticed.
Keywords: PCOS, Insulin receptor gene, GTT, lipid proteins, Iraqi female
Full-Text [PDF 169 kb]   (725 Downloads) |   |   Full-Text (HTML)  (369 Views)  
Type of Study: Original Article |
References
1. Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, et al. The androgen excess and PCOS society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril 2009; 91: 456-488. [DOI:10.1016/j.fertnstert.2008.06.035]
2. Legro RS, Bentley-Lewis R, Driscoll D, Wang SC, Dunaif A. Insulin resistance in the sisters of women with polycystic ovary syndrome: association with hyperandrogenemia rather than menstrual irregularity. J Clin Endocrinol Metab 2002; 87: 2128-2133. [DOI:10.1210/jcem.87.5.8513]
3. Urbanek M. The genetics of the polycystic ovary syndrome. Nat Clin Pract Endocrinol Metab 2007; 3: 103-111. [DOI:10.1038/ncpendmet0400]
4. Taira M, Hashimoto N. Insulin receptor abnormality and its clinical aspect. Nippon Rinsho 1998; 56: 1866-1870.
5. Tsilchorozidou T, Overton C, Conway GS. The pathophysiology of polycystic ovary syndrome. Clin Endocrinol (Oxf) 2004; 60: 1-17. [DOI:10.1046/j.1365-2265.2003.01842.x]
6. 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: 1979-1983.
7. Krook A, Kumar S, Laing I, Boulton AJ, Wass JA, O'Rahilly S. Molecular scanning of the insulin receptor gene in syndromes of insulin resistance. Diabetes 1994; 43: 357-368. [DOI:10.2337/diab.43.3.357]
8. Li M, Youngren JF, Dunaif A, Goldfine ID, Maddux BA, Zhang BB, et al. Decreased insulin receptor (IR) autophosphorylation in fibroblasts from patients with PCOS: effects of serine kinase inhibitors and IR activators. J Clin Endocrinol Metab 2002; 87: 4088-4093. [DOI:10.1210/jc.2002-020363]
9. 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: 1240-1243. [DOI:10.1016/S0015-0282(02)04241-3]
10. Diamanti-Kandarakis E, Papavassiliou AG. Molecular mechanisms of insulin resistance in polycystic ovary syndrom. Trends Mol Med 2006; 12: 324-332. [DOI:10.1016/j.molmed.2006.05.006]
11. San Millán JL, Cortón M, Villuendas G, Sancho J, Peral B, Escobar-Morreale HF. Association of polycystic ovary syndrome with genomic variants related to insulin resistance, type 2 diabetes mellitus, and obesity. J Clin Endocrinol Metab 2004; 89: 2640-2646. [DOI:10.1210/jc.2003-031252]
12. Panz VR, Ruff P, Joffe BI, Kedda MA, Seftel HC. SSCP analysis of the tyrosine kinase domain of the insulin receptor gene: polymorphisms detected in South African black and white subjects. Hum Genet 1996; 97: 438-440. [DOI:10.1007/BF02267063]
13. Tucci S, Futterweit W, Concepcion ES, Greenberg DA, Villanueva R, Davies TF, et al. Evidence for association of polycystic ovary syndrome in caucasian women with a marker at the insulin receptor gene locus. J Clin Endocrinol Metab 2001; 86: 446-449. [DOI:10.1210/jcem.86.1.7274]
14. 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: 582-585.
15. Lee EJ, Yoo KJ, Kim SJ, Lee SH, Choi DH, Cha KU, et al. Relationship between the C/T single nucleotide polymorphysim in Exon 17 of the Insulin Receptor Gene and Polycystic Ovary Syndrom. J Biol Sci 2005; 5: 832-836. [DOI:10.3923/jbs.2005.832.836]
16. Venkatesan AM, Dunaif A, Corbould A. Insulin resistance in polycystic ovary syndrome: progress and paradoxes. Recent Prog Horm Res 2001; 56: 295-308. [DOI:10.1210/rp.56.1.295]
17. Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev 1997; [DOI:10.1210/er.18.6.774]
18. 18: 774-800. 18.Musso C, Cochran E, Moran SA, Skarulis MC, Oral EA, Taylor S, et al. Clinical course of genetic diseases of the insulin receptor (type A and Rabson-Mendenhall syndromes): a 30-year prospective. Medicine (Baltimore) 2004; 83: 209-222. [DOI:10.1097/01.md.0000133625.73570.54]
19. Seeley RJ, Woods SC. Monitoring of stored and available fuel by the CNS: Implications for obesity. Nat Rev Neurosci 2003; 4: 901-909. [DOI:10.1038/nrn1245]
20. Pocai A, Lam TK, Obici S, Gutierrez-Juarez R, Muse ED, Arduini A, et al. Restoration of hypothalamic lipid sensing normalizes energy and glucose homeostasis in overfed rats. J Clin Invest 2006; 116: 1081-1091. [DOI:10.1172/JCI26640]
21. Murray RK, Granner DK, Mayes PA, Rodwell VW. Overview of Metabolism. In: Mayes P A and Bender D A (ed). Harper's Illustrated Biochemistry. 26th Ed. New York, Lange Medical Books/McGraw-Hill; 2003: 125.
22. Petersen KF, Shulman GI. Etiology of insulin resistance. Am J Med 2006; 119 (Suppl.): 10-16. [DOI:10.1016/j.amjmed.2006.01.009]
23. Paradis S, Ruvkun G. Caenorhabditis elegans Akt/PKB transduces insulin receptor-like signals from AGE-1 PI3 kinase to the DAF-16 transcription factor. Genes Dev 1998; 12: 2488-2498. [DOI:10.1101/gad.12.16.2488]
24. Gateva A, Kamenov Z. Cardiovascular Risk Factors in Bulgarian Patients with Polycystic Ovary Syndrome and/or Obesity. Obstet Gynecol Int 2012; ID: 306347.
25. Matthaei S, Stumvoll M, Kellerer M, Häring H. Pathophysiology and pharmacological treatment of insulin resistance. Endocr Rev 2000; 21: 585-618. [DOI:10.1210/er.21.6.585]
Send email to the article author

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Designed & Developed by : Yektaweb