Jsmc-10232

BIOMARKER ASSESSMENT OF SERUM INTERLEUKIN-18 TOGETHER WITH HOMOCYSTEINE FOR POLYCYSTIC OVARIAN SYNDROME 

Sakar Karem Abdulla a, Ban Mousa Rashid a, and Beston Faiek Nore b, c 

a Department of Clinical Biochemistry, College of Pharmacy, University of Sulaimani; Kurdistan Region/ Iraq. 

b Department of Medical Biochemistry, College of Medicine, University of Sulaimani; Kurdistan Region/ Iraq.

c Department of Health, Kurdistan Institution for Strategic Studies and Scientific Research, Sulaimani, Kurdistan Region/ Iraq. 

Submitted: 9/9/2019; Accepted: 6/11/2019; Published: 21/12/2019

DOI Link: https://doi.org/10.17656/jsmc.10232 

ABSTRACT

Background 

Polycystic ovary syndrome (PCOS) a complex endocrine disorder associated with reproductive disorders and metabolic dysfunctions, insulin resistance with compensatory hyperinsulinemia, obesity, endometrial carcinoma, and cardiovascular diseases. 

Objectives

This study aims to evaluate the levels of IL-18 and homocysteine in serum as a possible biomarker for cardiovascular disease in 150 cases positive with PCOS and in 150 negative control females.

Patients and Method

This study was a case-control study and serum samples randomly taken from 300 individuals (150 samples from patients with PCOS and 150 samples from healthy controls). Five milliliters of venous blood has been taken from each individual and the samples were analyzed for interleukin-18 and homocysteine by using enzyme-linked immunosorbent assay, hormones profile include LH, FSH, LH/FSH ratio, TSH, PRL, and Testosterone.

Results

We found that the average level of IL-18 and homocysteine in serum were 378.3 ±181.21 pg/ml and 10.36 ± 5.98 nmol/ml respectively in PCOS patients, while in the control group the values were 224.98± 131.885 pg/ml and 5.17± 5.24 nmol/ml respectively. 

Conclusions

The results show a highly significant difference (p-value < 0.001) and high serum concentration of IL-18 and homocysteine in PCOS as compared to the control group. Therefore, elevation of IL-18 combined with homocysteine is a selective indicator for higher risk of PCOS, which is closely related to cardiovascular abnormality as we have gated for this category of PCOS patients. 

KEYWORDS

Polycystic Ovarian Syndrome, Interleukin-18, Homocysteine, Cardiovascular Disease, Biomarker.

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. The Journal of clinical endocrinology and metabolism. 2004;89(6):2745-9. Epub 2004/06/08.

2. Asuncion M, Calvo RM, San Millan JL, Sancho J, Avila S, Escobar-Morreale HF. A prospective study of the prevalence of the polycystic ovary syndrome in unselected Caucasian women from Spain. The Journal of clinical endocrinology and metabolism. 2000;85(7):2434-8. Epub 2000/07/21.

3. March WA, Moore VM, Willson KJ, Phillips DI, Norman RJ, Davies MJ. The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria. Human reproduction (Oxford, England). 2010;25(2):544-51. Epub 2009/11/17.

4. Franks S, Gharani N, Waterworth D, Batty S, White D, Williamson R, et al. The genetic basis of polycystic ovary syndrome. Human reproduction (Oxford, England). 1997;12(12):2641-8. Epub 1998/02/10.

5. Franks S, McCarthy M. Genetics of ovarian disorders: polycystic ovary syndrome. Reviews in endocrine & metabolic disorders. 2004;5(1):69-76. Epub 2004/02/18.

6. Vink JM, Sadrzadeh S, Lambalk CB, Boomsma DI. Heritability of polycystic ovary syndrome in a Dutch twin-family study. The Journal of clinical endocrinology and metabolism. 2006;91(6):2100-4. Epub 2005/10/13.

7. Ali AT. Polycystic ovary syndrome and metabolic syndrome. Ceska gynekologie. 2015;80(4):279-89. Epub 2015/08/13.

8. Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, et al. Positions statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an Androgen Excess Society guideline. The Journal of clinical endocrinology and metabolism. 2006;91(11):4237-45. Epub 2006/08/31.

9. Escobar-Morreale HF, Asuncion M, Calvo RM, Sancho J, San Millan JL. Receiver operating characteristic analysis of the performance of basal serum hormone profiles for the diagnosis of polycystic ovary syndrome in epidemiological studies. European journal of endocrinology / European Federation of Endocrine Societies. 2001;145(5):619-24. Epub 2001/11/27.

10. Nair MK, Pappachan P, Balakrishnan S, Leena ML, George B, Russell PS. Menstrual irregularity and poly cystic ovarian syndrome among adolescent girls--a 2 year follow-up study. Indian journal of pediatrics. 2012;79 Suppl 1:S69-73. Epub 2011/07/20.

11. group REA-sPcw. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Human reproduction (Oxford, England). 2004;19(1):41-7. Epub 2003/12/23.

12. Baillargeon JP. Use of insulin sensitizers in polycystic ovarian syndrome. Curr Opin Investig Drugs. 2005;6(10):1012-22. Epub 2005/11/02.

13. Balen A. The pathophysiology of polycystic ovary syndrome: trying to understand PCOS and its endocrinology. Best practice & research Clinical obstetrics & gynaecology. 2004;18(5):685-706. Epub 2004/09/24.

14. Yildiz BO, Azziz R. The adrenal and polycystic ovary syndrome. Reviews in endocrine & metabolic disorders. 2007;8(4):331-42. Epub 2007/10/13.

15. Buggs C, Rosenfield RL. Polycystic ovary syndrome in adolescence. Endocrinology and metabolism clinics of North America. 2005;34(3):677-705, x. Epub 2005/08/09.

16. Quinkler M, Sinha B, Tomlinson JW, Bujalska IJ, Stewart PM, Arlt W. Androgen generation in adipose tissue in women with simple obesity--a site-specific role for 17beta-hydroxysteroid dehydrogenase type 5. The Journal of endocrinology. 2004;183(2):331-42. Epub 2004/11/09.

17. Fassnacht M, Schlenz N, Schneider SB, Wudy SA, Allolio B, Arlt W. Beyond adrenal and ovarian androgen generation: Increased peripheral 5 alpha-reductase activity in women with polycystic ovary syndrome. The Journal of clinical endocrinology and metabolism. 2003;88(6):2760-6. Epub 2003/06/06.

18. Vassiliadi DA, Barber TM, Hughes BA, McCarthy MI, Wass JA, Franks S, et al. Increased 5 alpha-reductase activity and adrenocortical drive in women with polycystic ovary syndrome. The Journal of clinical endocrinology and metabolism. 2009;94(9):3558-66. Epub 2009/07/02.

19. Lim SS, Norman RJ, Davies MJ, Moran LJ. The effect of obesity on polycystic ovary syndrome: a systematic review and meta-analysis. Obesity reviews : an official journal of the International Association for the Study of Obesity. 2013;14(2):95-109. Epub 2012/11/02.

20. Eagleson CA, Gingrich MB, Pastor CL, Arora TK, Burt CM, Evans WS, et al. Polycystic ovarian syndrome: evidence that flutamide restores sensitivity of the gonadotropin-releasing hormone pulse generator to inhibition by estradiol and progesterone. The Journal of clinical endocrinology and metabolism. 2000;85(11):4047-52. Epub 2000/11/30.

21. Orio F, Jr., Palomba S, Cascella T, Di Biase S, Manguso F, Tauchmanova L, et al. The increase of leukocytes as a new putative marker of low-grade chronic inflammation and early cardiovascular risk in polycystic ovary syndrome. The Journal of clinical endocrinology and metabolism. 2005;90(1):2-5. Epub 2004/10/16.

22. Dissen GA, Garcia-Rudaz C, Paredes A, Mayer C, Mayerhofer A, Ojeda SR. Excessive Ovarian Production of Nerve Growth Factor Facilitates Development of Cystic Ovarian Morphology in Mice and Is a Feature of Polycystic Ovarian Syndrome in Humans. Endocrinology. 2009;150(6): 2906–14.

23. Garlanda C, Dinarello CA, Mantovani A. The interleukin-1 family: back to the future. Immunity. 2013;39(6):1003-18. Epub 2013/12/18.

24. Bellora F, Castriconi R, Doni A, Cantoni C, Moretta L, Mantovani A, et al. M-CSF induces the expression of a membrane-bound form of IL-18 in a subset of human monocytes differentiating in vitro toward macrophages. European journal of immunology. 2012;42(6):1618-26. Epub 2012/06/09.

25. TW W, H A, M T, C K, EM H. Adipose tissue expression of interleukin-18 mRNA is elevated in subjects with metabolic syndrome and independently associated with fasting glucose. Wien Klin Wochenschr. 2011;123:650-4.

26. Gracie JA, Robertson SE, McInnes IB. Interleukin-18. Journal of leukocyte biology. 2003;73(2):213-24. Epub 2003/01/30.

27. Chandrasekar B, Marelli-Berg FM, Tone M, Bysani S, Prabhu SD, Murray DR. Beta-adrenergic stimulation induces interleukin-18 expression via beta2-AR, PI3K, Akt, IKK, and NF-kappaB. Biochemical and biophysical research communications. 2004;319(2):304-11. Epub 2004/06/05.

28. Sahar S, Dwarakanath RS, Reddy MA, Lanting L, Todorov I, Natarajan R. Angiotensin II enhances interleukin-18 mediated inflammatory gene expression in vascular smooth muscle cells: a novel cross-talk in the pathogenesis of atherosclerosis. Circulation research. 2005;96(10):1064-71. Epub 2005/04/30.

29. Nold M, Goede A, Eberhardt W, Pfeilschifter J, Muhl H. IL-18 initiates release of matrix metalloproteinase-9 from peripheral blood mononuclear cells without affecting tissue inhibitor of matrix metalloproteinases-1: suppression by TNF alpha blockage and modulation by IL-10. Naunyn-Schmiedeberg's archives of pharmacology. 2003;367(1):68-75. Epub 2003/03/05.

30. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA: a cancer journal for clinicians. 2012;62(1):10-29. Epub 2012/01/13.

31. H.Oku, Y.Tsuji, S.-I.Kashiwamura, S.Adachi, A.Kubota, H.Okamura, et al. Role of IL-18 in pathogenesis of endometriosis. Human Reproduction 2004;19:709-14.

32. Al-Khateeb GM, Sater MS, Finan RR, Mustafa FE, Al-Busaidi AS, Al-Sulaiti MA, et al. Analysis of interleukin-18 promoter polymorphisms and changes in interleukin-18 serum levels underscores the involvement of interleukin-18 in recurrent spontaneous miscarriage. Fertility and sterility. 2011;96(4):921-6. Epub 2011/08/16.

33. Nygard O, Vollset SE, Refsum H, Brattstrom L, Ueland PM. Total homocysteine and cardiovascular disease. Journal of internal medicine. 1999;246(5):425-54. Epub 1999/12/03.

34. Battistelli S, Vittoria A, Stefanoni M, Bing C, Roviello F. Total plasma homocysteine and methylenetetrahydrofolate reductase C677T polymorphism in patients with colorectal carcinoma. World J Gastroenterol. 2006;12(38):6128–32.

35. House JD, Jacobs RL, Stead LM, Brosnan ME, Brosnan JT. Regulation of homocysteine metabolism. Advances in enzyme regulation. 1999;39:69-91. Epub 1999/09/02.

36. McCarty MF. Insulin secretion as a potential determinant of homocysteine levels. Medical hypotheses. 2000;55(5):454-5. Epub 2000/11/03.

37. Escobar-Morreale HF, Botella-Carretero JI, Villuendas G, Sancho J, San Millan JL. Serum interleukin-18 concentrations are increased in the polycystic ovary syndrome: relationship to insulin resistance and to obesity. The Journal of clinical endocrinology and metabolism. 2004;89(2):806-11. Epub 2004/02/07.

38. Blankenberg S, Tiret L, Bickel C, Peetz D, Cambien F, Meyer J, et al. Interleukin-18 is a strong predictor of cardiovascular death in stable and unstable angina. Circulation. 2002;106(1):24-30. Epub 2002/07/03.

39. Loverro G, Lorusso F, Mei L, Depalo R, Cormio G, Selvaggi L. The plasma homocysteine levels are increased in polycystic ovary syndrome. Gynecologic and obstetric investigation. 2002;53(3):157-62. Epub 2002/06/08.

40. Randeva HS, Lewandowski KC, Drzewoski J, Brooke-Wavell K, O'Callaghan C, Czupryniak L, et al. Exercise decreases plasma total homocysteine in overweight young women with polycystic ovary syndrome. The Journal of clinical endocrinology and metabolism. 2002;87(10):4496-501. Epub 2002/10/05.

41. Vrbikova J, Bicikova M, Tallova J, Hill M, Starka L. Homocysteine and steroids levels in metformin treated women with polycystic ovary syndrome. Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association. 2002;110(2):74-6. Epub 2002/04/03.

42. Schachter M, Raziel A, Friedler S, Strassburger D, Bern O, Ron-El R. Insulin resistance in patients with polycystic ovary syndrome is associated with elevated plasma homocysteine. Human reproduction (Oxford, England). 2003;18(4):721-7. Epub 2003/03/28.

43. Wijeyaratne CN, Nirantharakumar K, Balen AH, Barth JH, Sheriff R, Belchetz PE. Plasma homocysteine in polycystic ovary syndrome: does it correlate with insulin resistance and ethnicity? Clinical endocrinology. 2004;60(5):560-7. Epub 2004/04/24.

44. Lakshmikumar K, Gomti KD, Shugeta ND, Arbind RS. Effect of age on serum homocysteine level among adult urban population of Manipur. 2013;27(1):46-8.

45. Schachter1 M, Raziel A, Friedler S, Strassburger D, and OB, Ron-El R. Insulin resistance in patients with polycystic ovary syndrome is associated with elevated plasma homocysteine. Human Reproduction. 2003;18(4):721-7.

46. Gareeb AIA-, Amieer WSAA-, Alkuraishy HM, Mayahi TJA-. Effect of body weight on serum homocysteine level in patients with polycystic ovarian syndrome: A case control study. Int J Reprod Biomed 2016;14(2):81-8.

47. Atamer A, Demir B, Bayhan G, Atamer DY, Ilhan N, Akkuş Z. Serum Levels of Leptin and Homocysteine in Women with Polycystic Ovary Syndrome and Its Relationship to Endocrine, Clinical and Metabolic Parameters. 2008;36(1):96-105.

48. Gul OB, Somunkiran A, Yucel O, Demirci F, Ozdemir I. The effect of ethinyl estradiol-cyproterone acetate treatment on homocysteine levels in women with polycystic ovary syndrome. Archives of gynecology and obstetrics. 2008;277(1):25-30. Epub 2007/07/10.

49. Fulghesu AM, Cucinelli F, Pavone V, Murgia F, Guido M, Caruso A, et al. Changes in luteinizing hormone and insulin secretion in polycystic ovarian syndrome. Human reproduction (Oxford, England). 1999;14(3):611-7. Epub 1999/04/30.

50. Suresh.S, Vijayakumar.T. Correlations of Insulin Resistance and Serum Testosterone Levels with LH:FSH Ratio and Oxidative Stress in Women with Functional Ovarian Hyperandrogenism. Indian J Clin Biochem 2015;30(3):345-50.

Full Text

 © The Authors, published by University of Sulaimani, College of Medicine

This work is licensed under a Creative Commons Attribution 4.0 International License.