Skip to main content
Log in

Association of Genetic Polymorphisms in TNF and MIF Gene with the Risk of Primary Dysmenorrhea

  • Original Article
  • Published:
Biochemical Genetics Aims and scope Submit manuscript

Abstract

Primary dysmenorrhea, which affects 90 % of adolescent girls and more than 50 % of menstruating women worldwide, is characterized by recurrent pain during menses in the absence of a detectable organic disease. The aim of this study is to assess the association between MIF −173 and TNF −308 genetic polymorphisms and the clinical features of primary dysmenorrhea. The study population comprised 154 unrelated female patients with clinical diagnosis of dysmenorrhea, and a total of 144 control subjects were recruited consecutively. The MIF 173G > C promoter polymorphism (rs755622) and TNF gene −308G > A (rs1800629) polymorphism were analyzed by polymerase chain reaction-based restriction fragment length polymorphism assay. Two fragments (268 and 97 bp) were seen when the G allele was present at position –173, and three fragments (206, 97, and 62 bp) were observed when the C allele was present. Two fragments (87 and 20 bp) were seen when G allele was present at position −308. There were statistically significant associations between age at menarche and history of back pain among dysmenorrhea patients and MIF gene −173G > C polymorphism (p = 0.003 and p = 0.042, respectively). The genotype and allele frequencies of −308G > A polymorphism showed statistically significant differences between dysmenorrhea patients and controls (p = 0.023 and p = 0.009, respectively). A high association was also observed when the patients were compared with the controls according to the GG genotype versus GA+AA genotypes (p = 0.009). The present study showed that the TNF-α −308 GG genotype may be a useful tool to predict the susceptibility of dysmenorrhea.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Abraham LJ, Kroeger KM (1999) Impact of the -308 TNF promoter polymorphism on the transcriptional regulation of the TNF gene: relevance to disease. J Leukoc Biol 66:562–566

    CAS  PubMed  Google Scholar 

  • Abu JI, Konje JC (2000) Leukotrienes in gynaecology: the hypothetical value of anti-leukotriene therapy in dysmenorrhoea and endometriosis. Hum Reprod Update 6:200–205

    Article  CAS  PubMed  Google Scholar 

  • Berkley KJ (2013) Primary dysmenorrhea: an urgent mandate. Pain 21:1–8

    Google Scholar 

  • Bernhagen J, Bacher M, Calandra T, Metz CN, Doty SB, Donnelly T, Bucala R (1996) An essential role for macrophage migration inhibitory factor in the tuberculin delayed-type hypersensitivity reaction. J Exp Med 183:277–282

    Article  CAS  PubMed  Google Scholar 

  • Bucala R (2013) MIF, MIF alleles, and prospects for therapeutic intervention in autoimmunity. J Clin Immunol 33:72–78

    Article  CAS  Google Scholar 

  • Calandra T, Roger T (2003) Macrophage migration inhibitory factor: a regulator of innate immunity. Nat Rev Immunol 3:791–800

    Article  CAS  PubMed  Google Scholar 

  • Cui G, Wang H, Li R, Zhang L, Li Z, Wang Y, Hui R, Ding H, Wang DW (2012) Polymorphism of tumor necrosis factor alpha (TNF-alpha) gene promoter, circulating TNF-alpha level, and cardiovascular risk factor for ischemic stroke. J Neuroinflammation 9:235

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Donn RP, Shelley E, Oilier WE, Thomson W (2001) A novel 50- flanking region polymorphism of macrophage migration inhibitory factor is associated with systemic-onset juvenile idiopathic arthritis. Arthritis Rheum 44:1782–1785

    Article  CAS  PubMed  Google Scholar 

  • Elahi MM, Asotra K, Matata BM, Mastana SS (2009) Tumor necrosis factor alpha −308 gene locus promoter polymorphism: an analysis of association with health and disease. Biochim Biophys Acta 1792:163–172

    Article  CAS  PubMed  Google Scholar 

  • Fedorowicz Z, Nasser M, Jagannath VA, Beaman JH, Ejaz K, van Zuuren EJ (2012) Beta2-adrenoceptor agonists for dysmenorrhoea. Cochrane Database Syst Rev 5:Cd008585

    Google Scholar 

  • Fei BY, Lv HX, Yang JM, Ye ZY (2008) Association of MIF-173 gene polymorphism with inflammatory bowel disease in Chinese Han population. Cytokine 41:44–47

    Article  CAS  PubMed  Google Scholar 

  • French L (2005) Dysmenorrhea. Am Fam Physician 71:285–291

    PubMed  Google Scholar 

  • Harada T (2013) Dysmenorrhea and endometriosis in young women. Yonago Acta Med 56:81–84

    PubMed  PubMed Central  Google Scholar 

  • Karakaya B, van Moorsel CH, van der Helm-van Mil AH, Huizinga TW, Ruven HJ, van der Vis JJ, Grutters JC (2014) Macrophage migration inhibitory factor (MIF) -173 polymorphism is associated with clinical erythema nodosum in Löfgren’s syndrome. Cytokine 69:272–276

    Article  CAS  PubMed  Google Scholar 

  • Ma H, Hong M, Duan J, Liu P, Fan X, Shang E, Su S, Guo J, Qian D, Tang Y (2013) Altered cytokine gene expression in peripheral blood monocytes across the menstrual cycle in primary dysmenorrhea: a case-control study. PLoS One 8:e55200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nicoletti F, Creange A, Orlikowski D, Bolgert F, Mangano K, Metz C, Di Marco R, Al Abed Y (2005) Macrophage migration inhibitory factor (MIF) seems crucially involved in Guillain-Barre syndrome and experimental allergic neuritis. J Neuroimmunol 168:168–174

    Article  CAS  PubMed  Google Scholar 

  • Nishihira J, Ishibashi T, Fukushima T, Sun B, Sato Y, Todo S (2003) Macrophage migration inhibitory factor (MIF): its potential role in tumor growth and tumor-associated angiogenesis. Ann N Y Acad Sci 995:171–182

    Article  CAS  PubMed  Google Scholar 

  • Pociot F, Wilson AG, Nerup J, Duff GW (1993) No independent association between a tumor necrosis factor-alpha promotor region polymorphism and insulin-dependent diabetes mellitus. Eur J Immunol 23:3050–3053

    Article  CAS  PubMed  Google Scholar 

  • Renner P, Roger T, Calandra T (2005) Macrophage migration inhibitory factor: gene polymorphisms and susceptibility to inflammatory diseases. Clin Infect Dis 41:513–519

    Article  Google Scholar 

  • Rigante D, Flex A, Federico G, Pola R, Candelli M, Manna R, Pugliese AL, Cerquaglia C, Compagnone A, Stabile A (2007) Serum macrophage migration inhibitory factor (MIF) in the intercritical phase of hereditary periodic fevers and its relationship with the MIF-173G/C polymorphism. Scand J Rheumatol 36:307–310

    Article  CAS  PubMed  Google Scholar 

  • Treloar SA, Martin NG, Heath AC (1998) Longitudinal genetic analysis of menstrual flow, pain, and limitation in a sample of Australian twins. Behav Genet 28:107–116

    Article  CAS  PubMed  Google Scholar 

  • Von Wolff M, Thaler CJ, Strowitzki T, Broome J, Stolz W, Tabibzadeh S (2000) Regulated expression of cytokines in human endometrium throughout the menstrual cycle: dysregulation in habitual abortion. Mol Hum Reprod 6:627–634

    Article  Google Scholar 

  • Wang FF, Huang XF, Shen N, Leng L, Bucala R, Chen SL, Lu LJ (2013) A genetic role for macrophage migration inhibitory factor (MIF) in adult-onset Still’s disease. Arthritis Res Ther 15:R65

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Authors’ Contributions

H Yilmaz Dogru conceived the idea, designed and drafted the manuscript and figures. AZ Ozsoy conceived the initial idea and developed the project. N Karakus, IB Delibas, C Kunt Isguder, and S Yigit collected and analyzed the data, wrote the manuscript, and developed the illustrations and figures.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hatice Yilmaz Dogru.

Ethics declarations

Conflict of interests

The authors declare that they have no conflict of interest.

Disclosure

The authors declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence their work; there is no professional or other personal interest of any nature or kind in any product, service, and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled.

Ethical Approval

The study protocol had been approved by The Clinical Research Ethical Committee of Gaziosmanpasa University.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dogru, H.Y., Ozsoy, A.Z., Karakus, N. et al. Association of Genetic Polymorphisms in TNF and MIF Gene with the Risk of Primary Dysmenorrhea. Biochem Genet 54, 457–466 (2016). https://doi.org/10.1007/s10528-016-9732-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10528-016-9732-2

Keywords

Navigation