Association Between the -1031 (T/C) Polymorphism of TNF-α Gene and Biochemical Factors in Women With Polycystic Ovary Syndrome

authors:

avatar Mehdi Sahmani 1 , avatar Talaate Dabaghi Ghaleh 2 , avatar Maryam Yargholi 2 , avatar Farshad Foroughi 3 , avatar Amir Javadi ORCID 4 , * , avatar Khadijeh Taherkhani 5

Department of Biochemistry, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.
Department of Obstetrics and Gynecology, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.
Department of Immunology, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.
Medical Microbiology Research Center, Qazvin University of Medical Sciences, Qazvin, Iran.
Cellular and Molecular Research Center, Qazvin University of Medical Sciences, Qazvin, Iran.
Journal of Inflammatory Diseases: Vol.24, issue 6; 486-497
article type: issue_documents_importer

How To Cite Sahmani M, Dabaghi Ghaleh T, Yargholi M, Foroughi F, Javadi A, et al. Association Between the -1031 (T/C) Polymorphism of TNF-α Gene and Biochemical Factors in Women With Polycystic Ovary Syndrome. J Inflamm Dis. 2021;24(6):e156249. 

Abstract

Background: Tumor Necrosis Factor Alpha (TNF-α) gene, as an inflammatory factor, plays an important role in reproductive physiology, especially in women with Polycystic Ovary Syndrome (PCOS). Objective: This study aims to investigate the relationship between the -1031 T/C polymorphism of TNF-α gene and biochemical factors in women with PCOS. Methods: In this case-control study, participants were 106 women with PCOS and 114 healthy women referred to Kosar Hospital in Qazvin, Iran. The TNF-α gene’s polymorphism was determined using Polymerase Chain Reaction (PCR) technique and PCR-Restriction Fragment Length Polymorphism (PCR-RFLP) method. Biochemical factors of serum levels were also measured in two groups. Logistic regression analysis examined the relationship between the frequency of alleles in different states and the risk of PCOS. Findings: There were statistically significant difference in the mean levels of total cholesterol, triglycerides, testosterone, two-hour blood glucose and body mass index between the groups, whose values were higher in women with PCOS compared to healthy women (P<0.001). In women with PCOS, the mean serum levels of triglyceride and high-density lipoprotein were significantly different between the three TT, CC, TC genotypes of TNF-α gene polymorphism (P<0.05). The results of regression analysis showed that the TT genotype had significant association with the risk of PCOS (OR=2.43, P=0.006, 95%CI: 1.28-2.62). Conclusion: It seems that there is a relationship between the -1301 (T/C) polymorphism of TNF-α gene and the risk of PCOS in women.

References

  • 1.

    McCartney CR, Marshall JC. Clinical practice. Polycystic Ovary Syndrome. N Engl J Med. 2016; 375(1):54-64. [DOI:10.1056/ NEJMcp1514916] [PMID] [PMCID].

  • 2.

    Yildiz BO, Bozdag G, Yapici Z, Esinler I, Yarali H. Prevalence, phenotype and cardiometabolic risk of polycystic ovary syndrome under different diagnostic criteria. Hum Reprod. 2012; 27(10):3067-73. [DOI:10.1093/humrep/des232] [PMID].

  • 3.

    Li S, Zhu D, Duan H, Tan Q. The epigenomics of polycystic ovarian syndrome: From pathogenesis to clinical manifestations. Gynecol Endocrinol. 2016; 32(12):942-6. [DOI:10.1080/09513 590.2016.1203409] [PMID].

  • 4.

    Sahmani M, Dabbaghi Ghaleh T, Darabi M, Darabi M, Rashvand Z, Najafipour R. I405V polymorphism of CETP gene and lipid profile in women with endometriosis. Gynecol Endocrinol. 2013; 29(7):712-5. [DOI:10.3109/09513590.2013.797396] [PMID].

  • 5.

    Ajmal N, Khan SZ, Shaikh R. Polycystic Ovary Syndrome (PCOS) and genetic predisposition: A review article. Eur J Obstet Gynecol Reprod Biol X. 2019; 3:100060. [DOI:10.1016/j.eurox. 2019.100060] [PMID] [PMCID].

  • 6.

    Franks S, McCarthy M. Genetics of ovarian disorders: Polycystic ovary syndrome. Rev Endocr Metab Disord. 2004; 5(1):69- 76. [DOI:10.1023/B:REMD.0000016125.05878.96] [PMID].

  • 7.

    De Leo V, Musacchio MC, Cappelli V, Massaro MG, Morgante G, Petraglia F. Genetic, hormonal and metabolic aspects of PCOS: An update. Reprod Biol Endocrinol. 2016; 14(1):38. [DOI:10.1186/s12958-016-0173-x] [PMID] [PMCID].

  • 8.

    Joseph Sh, Barai RS, Bhujbalrao R, Idicula-Thomas S. PCOSKB: A KnowledgeBase on genes, diseases, ontology terms and biochemical pathways associated with PolyCystic Ovary Syndrome. Nucleic Acids Res. 2016; 44(D1):D1032-5. [DOI:10.1093/nar/gkv1146] [PMID] [PMCID].

  • 9.

    Willrich MA, Murray DL, Snyder MR. Tumor necrosis factor inhibitors: Clinical utility in autoimmune diseases. Transl Res. 2015; 165(2):270-82. [DOI:10.1016/j.trsl.2014.09.006] [PMID].

  • 10.

    Saha P, Smith A. TNF- (Tumor Necrosis Factor-). Arterioscler Thromb Vasc Biol. 2018; 38(11):2542-3. [DOI:10.1161/ ATVBAHA.118.311660] [PMID].

  • 11.

    Yun JH, Choi JW, Lee KJ, Shin JS, Baek KH. The promoter -1031(T/C) polymorphism in tumor necrosis factor-alpha associated with polycystic ovary syndrome. Reprod Biol Endocrinol. 2011; 9:131. [DOI:10.1186/1477-7827-9-131] [PMID] [PMCID].

  • 12.

    Japur CC, Diez-Garcia RW, de Oliveira Penaforte FR, das Graas Pena G, de Arajo LB, de S MFS. Insulin, ghrelin and early return of hunger in women with obesity and polycystic ovary syndrome. Physiol Behav. 2019; 206:252-8. [DOI:10.1016/j. physbeh.2019.03.013] [PMID].

  • 13.

    Panidis D, Farmakiotis D, Koliakos G, Rousso D, Kourtis A, Katsikis I, et al. Comparative study of plasma ghrelin levels in women with polycystic ovary syndrome, in hyperandrogenic women and in normal controls. Hum Reprod. 2005; 20(8):2127-32. [DOI:10.1093/humrep/dei055] [PMID].

  • 14.

    Choi HJ, Cho YM, Moon MK, Choi HH, Shin HD, Jang HC, et al. Polymorphisms in the ghrelin gene are associated with serum high-density lipoprotein cholesterol level and not with type 2 diabetes mellitus in Koreans. J Clin Endocrinol Metab. 2006;91(11):4657-63. [DOI:10.1210/jc.2005-2549] [PMID].

  • 15.

    Rosenfield RL, Ehrmann DA. The Pathogenesis of Polycystic Ovary Syndrome (PCOS): The hypothesis of PCOS as functional ovarian hyperandrogenism revisited. Endocr Rev. 2016; 37(5):467-520. [DOI:10.1210/er.2015-1104] [PMID] [PMCID].

  • 16.

    Brynskov J, Foegh P, Pedersen G, Ellervik C, Kirkegaard T, Bingham A, et al. Tumour necrosis factor alpha converting enzyme (TACE) activity in the colonic mucosa of patients with inflammatory bowel disease. Gut. 2002; 51(1):37-43. [DOI:10.1136/ gut.51.1.37] [PMID] [PMCID].

  • 17.

    Zore T, Joshi NV, Lizneva D, Azziz R. Polycystic Ovarian Syndrome: Long-term health consequences. Semin Reprod Med. 2017; 35(3):271-81. [DOI:10.1055/s-0037-1603096] [PMID].

  • 18.

    Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972; 18(6):499-502. [DOI:10.1093/clinchem/18.6.499] [PMID].

  • 19.

    St-Pierre DH, Karelis AD, Coderre L, Malita F, Fontaine J, Mignault D, et al. Association of acylated and nonacylated ghrelin with insulin sensitivity in overweight and obese postmenopausal women. J Clin Endocrinol Metab. 2007; 92(1):264-9. [DOI:10.1210/jc.2006-1603] [PMID].

  • 20.

    Drakou A, Mavrogianni D, Ntzeros K, Protopapas A, Drakakis P, Loutradis D. Association between tumor necrosis factor- gene-1031T/C promoter polymorphism and endometriosis in a European population. Horm Mol Biol Clin Investig. 2019; 40(2):20190033. [DOI:10.1515/hmbci-2019-0033] [PMID].

  • 21.

    Milner CR, Craig JE, Hussey ND, Norman RJ. No association between the -308 polymorphism in the Tumour Necrosis Factor alpha (TNFalpha) promoter region and polycystic ovaries. Mol Hum Reprod. 1999; 5(1):5-9. [DOI:10.1093/molehr/5.1.5][PMID].

  • 22.

    Abutorabi R, Baradaran A, Sadat Mostafavi F, Zarrin Y, Mardanian F. Evaluation of tumor necrosis factor alpha polymorphism frequencies in endometriosis. Int J Fertil Steril. 2015; 9(3):329-37. [DOI:10.22074/ijfs.2015.4548] [PMID] [PMCID].

  • 23.

    Lizneva D, Suturina L, Walker W, Brakta S, Gavrilova-Jordan L, Azziz R. Criteria, prevalence, and phenotypes of polycystic ovary syndrome. Fertil Steril. 2016; 106(1):6-15. [DOI:10.1016/j. fertnstert.2016.05.003] [PMID].

  • 24.

    Kenigsberg LE, Agarwal C, Sin S, Shifteh K, Isasi CR, Crespi R, et al. Clinical utility of magnetic resonance imaging and ultrasonography for diagnosis of polycystic ovary syndrome in adolescent girls. Fertil Steril. 2015; 104(5):1302-9.e1-4. [DOI:10.1016/j.fertnstert.2015.08.002] [PMID] [PMCID].

  • 25.

    Taghavi SA, Bazarganipour F, Allan H, Khashavi Z, Reisi N, Dosha N, et al. Pelvic floor dysfunction and polycystic ovary syndrome. Hum Fertil. 2017; 20(4):262-7. [DOI:10.1080/1464727 3.2017.1292003] [PMID].

  • 26.

    Baptiste CG, Battista MC, Trottier A, Baillargeon JP. Insulin and hyperandrogenism in women with polycystic ovary syndrome. J Steroid Biochem Mol Biol. 2010; 122(1-3):42-52. [DOI:10.1016/j.jsbmb.2009.12.010] [PMID] [PMCID].

  • 27.

    Joham AE, Palomba S, Hart R. Polycystic Ovary Syndrome, obesity, and pregnancy. Semin Reprod Med. 2016; 34(2):93-101. [DOI:10.1055/s-0035-1571195] [PMID].

  • 28.

    Ando T, Ichimaru Y, Konjiki F, Shoji M, Komaki G. Variations in the preproghrelin gene correlate with higher body mass index, fat mass, and body dissatisfaction in young Japanese women. Am J Clin Nutr. 2007; 86(1):25-32. [DOI:10.1093/ajcn/86.1.25[PMID].

  • 29.

    Glueck CJ, Goldenberg N. Characteristics of obesity in polycystic ovary syndrome: Etiology, treatment, and genetics. Metabolism. 2019; 92:108-20. [DOI:10.1016/j.metabol.2018.11.002] [PMID].

  • 30.

    Dumesic DA, Oberfield SE, Stener-Victorin E, Marshall JC, Laven JS, Legro RS. Scientific statement on the diagnostic criteria, epidemiology, pathophysiology, and molecular genetics of polycystic ovary syndrome. Endocr Rev. 2015; 36(5):487-525. [DOI:10.1210/er.2015-1018] [PMID] [PMCID].

  • 31.

    Gu HF, Mou M, Liang ZG, Sun C, Ren XY, Xiao YB. The association between paraoxonase 1 gene polymorphisms and polycystic ovarian syndrome. Cell Mol Biol (Noisy-le-grand). 2016; 62(14):44-7. [PMID].

  • 32.

    Giandalia A, Pappalardo MA, Russo GT, Romeo EL, Alibrandi A, Di Bari F, et al. Influence of peroxisome proliferator-activated receptor- exon 2 and exon 6 and Insulin Receptor Substrate (IRS)-1 Gly972Arg polymorphisms on insulin resistance and beta-cell function in Southern Mediterranean women with polycystic ovary syndrome. J Clin Transl Endocrinol. 2018; 13:1-8 [DOI:10.1016/j.jcte.2018.05.002] [PMID] [PMCID]##.