DOI QR코드

DOI QR Code

The ICAM-1 Gly241Arg Polymorphism is Not Associated With Polycystic Ovary Syndrome - Results from a Case Control study in Kashmir, India

  • Published : 2016.04.11

Abstract

Background: Polycystic ovary syndrome (PCOS) is considered to be a multifactorial disorder resulting from the interaction of several predisposing and protective genetic variants. PCOS is associated with low-grade chronic inflammation. Elevated levels of inflammatory markers including intercellular adhesion molecule-1 (ICAM-1) are demonstrated in women with PCOS. Recent evidence indicates a significant linkage between a locus on chromosome 19p13 and multifactorial diseases that have an inflammatory component. The aim of the study was to assess the possible association of Gly241Arg polymorphism of ICAM-1 gene located on chromosome 19p13 in determining risk of PCOS in Kashmiri women. Materials and Methods: Gly241Arg SNP in DNA from peripheral blood leukocytes of 220 PCOS cases and 220 age matched non-PCOS healthy controls was analysed using allel specific PCR. Results: The genotype and allele frequency distributions of Gly241Arg SNP showed insignificant difference between the PCOS cases and control women, indicating no role of this SNP in PCOS susceptibility. The odds ratio for Arg/Arg genotype was 0.87 (95% CI=0.32-2.3) [P=0.79], for Gly/Arg genotype was 0.98 (95% CI= 0.66-1.47) [P=1] and for Arg/Arg+Gly/Arg genotype was 0.97 (95% CI=0.65-1.45) [P=0.92]. The genotypic frequencies of ICAM-1codon 241 showed statistically insignificant difference between cases and controls (${\chi}^2=0.07$; p=0.96) Nor the studied polymorphism was found to affect clinical and laboratory parameters significantly. Conclusions: Although Gly241Arg polymorphism have not shown significant association with PCOS. Further, specifically designed studies on large cohorts are required to conclusively establish any role of ICAM-1 gene polymorphisms in PCOS in our study.

Keywords

References

  1. Asante A, Omurtag K, Stewart EA, Coddington CC (2015). Screening for insulin resistance in polycystic ovary syndrome: views of Physician Members of the American Society for Reproductive Medicine. J Reprod Med, 60, 371-7.
  2. Azziz R, Woods KS, Reyna R, et al (2004). The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab, 89, 2745-9. https://doi.org/10.1210/jc.2003-032046
  3. Blankenberg S, Barbaux S, Tiret L (2003). Adhesion molecules and atherosclerosis. Atherosclerosis, 170, 191-03. https://doi.org/10.1016/S0021-9150(03)00097-2
  4. Chou CH, Ueng KC, Liu YF, Wu CH, et al (2015). Impact of intercellular adhesion molecule-1 genetic polymorphisms on coronary artery disease susceptibility in taiwanese subjects. Int J Med Sci, 12, 510-6. https://doi.org/10.7150/ijms.12097
  5. Diamanti-Kandarakis E, Alexandraki K, Piperi C, et al (2006). Inflammatory and endothelial markers in women with polycystic ovary syndrome. Eur J Clin Invest, 36, 691-7. https://doi.org/10.1111/j.1365-2362.2006.01712.x
  6. Flex A, Gaetani E, Angelini F, et al (2007). Pro-inflammatory genetic profiles in subjects with peripheral arterial occlusive disease and critical limb ischemia. J Intern Med, 262, 124-30. https://doi.org/10.1111/j.1365-2796.2007.01791.x
  7. Gonzalez F, Rote NS, Minium J, et al (2009). Evidence of Proatherogenic inflammation in polycystic ovary syndrome. Metabolism, 58, 954-62. https://doi.org/10.1016/j.metabol.2009.02.022
  8. Hayflick JS, Kilgannon P, Gallatin WM (1998). The intercellular adhesion molecule (ICAM) family of proteins. New members and novel functions. Immunol Res, 17, 313-27. https://doi.org/10.1007/BF02786454
  9. Hazwanie H, Gan SY (2015). The relevance of genetic polymorphism of CYP1A1, ICAM-1, TNF-${\alpha}$ and INSR genes in women with polycystic ovary syndrome (PCOS). J Med Bioengineer, 4, 367-70. https://doi.org/10.12720/jomb.4.5.367-370
  10. Holder AL, Wolf S, Walshe S, et al (2008). Expression of endothelial intercellular adhesion molecule-1 is determined by genotype: effects on efficiency of leukocyte adhesion to human endothelial cells. Hum Immonol, 69, 71-8 https://doi.org/10.1016/j.humimm.2007.12.004
  11. Kanmaz-Ozer M, Vural P, Dogru-Abbasoglu S, et al (2012). Polymorphisms of vascular cell adhesion molecule 1(VCAM1) in polycystic ovary syndrome determined by quantitative real-time polymerase chain reaction and melting curve analysis. Eur J Obstet Gynecol Reprod Biol, 160, 174-78. https://doi.org/10.1016/j.ejogrb.2011.11.013
  12. Languino LR, Plescia J, Duperray A, et al (1993). Fibrinogen mediates leukocyte adhesion to vascular endothelium through an ICAM-1-dependent pathway. Cell, 73, 1423-34. https://doi.org/10.1016/0092-8674(93)90367-Y
  13. Lee EJ, Oh B, Lee JY, et al (2008). Association study between single nucleotide polymorphisms in the VEGF gene and polycystic ovary syndrome. Fertil Steril, 9, 1751-59.
  14. Mc Glinchey PG, Spence MS, Patterson CC, et al (2004). The intercellular adhesion molecule-1 (ICAM-1) gene K469E polymorphism is not associated with ischaemic heart disease: an investigation using family-based tests of association. Eur J Immunogenet, 31, 201-6. https://doi.org/10.1111/j.1365-2370.2004.00474.x
  15. Mycko MP, Kwinkowski M, Tronczynska E,(1998). Multiple sclerosis: the increased frequency of the ICAM-1 exon 6 gene point mutation genetic type K469. Ann Neurol, 44, 70-5. https://doi.org/10.1002/ana.410440113
  16. Nasiek M, Kos-Kudla B, Ostrowska Z, et al (2004). Plasma concentration of soluble intercellular adhesion molecule-1 in women with polycystic ovary syndrome. Gynecol Endocrinol, 19, 208-15. https://doi.org/10.1080/09513590400014313
  17. Nejentsev S, Guja C, McCormack R, Cooper J, et al (2003). Association of intercellular adhesion molecule-1 gene with type 1 diabetes. Lancet, 362, 1723-4. https://doi.org/10.1016/S0140-6736(03)14847-7
  18. Nidhi R, Padmalatha V, Nagarathna R, et al (2011). Prevalence of polycystic ovarian syndrome in Indian adolescents. J Pediatr Adolesc Gynecol, 24, 223-7. https://doi.org/10.1016/j.jpag.2011.03.002
  19. Ojeda-Ojeda M, Martinez-Garcia MA, Alpanes M, et al (2015). Association of TLR2 S450S and ICAM1 K469E polymorphisms with polycystic ovary syndrome (PCOS) and obesity. J Reproductive Immunol, 113, 9-15.
  20. Petrovic MG, Osredkar J, Saraga-Babic M, et al (2008). K469E polymorphism of intercellular adhesion molecule-1 gene is associated with proliferative diabetic retinopathy in Caucasians with type 2 diabetes. Clin Exp Ophthalmol, 36, 468-72. https://doi.org/10.1111/j.1442-9071.2008.01785.x
  21. Prieto D, Contreras C, Sanchez A (2014).Endothelial dysfunction, obesity and insulin resistance. Curr Vasc Pharmacol, 12, 412-26. https://doi.org/10.2174/1570161112666140423221008
  22. Rosenfield RL (2015). The Diagnosis of Polycystic Ovary Syndrome in Adolescents. Pediatrics, 136, 1154-65. https://doi.org/10.1542/peds.2015-1430
  23. Salvarani C, Casali B, Boiardi L (2000). Intercellular adhesion molecule 1 gene polymorphisms in polymyalgia rheumatica/giant cell arteritis: association with disease risk and severity. J Rheumatol, 27, 1215-21.
  24. Shen CC, Yang AC, Hung JH, Hu LY, Tsai SJ (2015). A nationwide population-based retrospective cohort study of the risk of uterine, ovarian and breast cancer in women with polycystic ovary syndrome. Oncologist, 20, 45-9. https://doi.org/10.1634/theoncologist.2014-0311
  25. Song GG, Lee YH (2015). The polymorphisms K469E and G261R of intercellular adhesion molecule-1 and susceptibility to inflammatory bowel disease: a meta-analysis. Immunol Invest, 44, 361-72. https://doi.org/10.3109/08820139.2015.1010685
  26. Springer TA (1990). Adhesion receptors of the immune system. Nature, 346, 425-34. https://doi.org/10.1038/346425a0
  27. Urbanek M, Woodroffe A, Ewens KG, et al (2005). Candidate gene region for polycystic ovary syndrome on chromosome 19p13.2. J Clin Endocrinol Metab, 90, 6623-9. https://doi.org/10.1210/jc.2005-0622
  28. Verity DH, Vaughan RW, Kondeatis E (2000).Intercellular adhesion molecule-1 gene polymorphisms in Behcet’s disease. Eur J Immunogenet, 27, 73-6. https://doi.org/10.1046/j.1365-2370.2000.00202.x
  29. Vora DK, Rosenbloom CL, Beaud AL, et al (1994). Polymorphisms and linkage analysis for ICAM-1 and the selectin gene cluster. Genomics, 21, 473-7. https://doi.org/10.1006/geno.1994.1303
  30. Vrbikova J (2005). Intercellular cell adhesion molecule-1 in PCOS; relation to insulin resistance or obesity. Endocrine Abstract, 9, 76.
  31. Vural P, Kanmaz-Ozer M, Dogru-Abbasoglu S, et al (2011). Lack of association between intercellular adhesion molecule-1 (ICAM-1) polymorphisms and polycystic ovary syndrome. J Assist Reprod Genet, 28, 869-75. https://doi.org/10.1007/s10815-011-9607-8