Objective:To explore whether having the mutant tumor necrosis factor (TNF)2 (G-308*A) and TNFA-A (G-238*A) alleles in the TNF-α gene promotor region is higher in women with endometriosis, we determined the respective genotype and allele frequencies in a retrospective case-control study.
Methods:Polymerase chain reaction was performed to identify the G-308A and G-238A promotor polymorphisms in 92 women with surgically and histologically confirmed endometriosis. A series of 69 healthy women without a history of endometriosis served as clinical controls.
Results:The allele frequnecies of the TNF2 polymorphism were 0.13 and 0.16 in women with endometriosis and in the control group, respectively, and the frequencies of the TNFA-A polymorphisms in women with endometrisosis and in the control group were 0.04 and 0.05, respectively, with no significant difference between the study and control groups. The TNF2 polymorphism was present in the homozygous form (TNF2/2) in 4.3% of women with endometriosis and in 2.9% of controls (P = .7). No TNFA-A homozygotes (TNFAA/A) were detected.
Conclusion:We studied TNF-α promotor gene variants among women with endometriosis and found that having the G-308A TNF-α and the G-238A TNF-α polymorphism was not associated with endometriosis in a white population.
1. Olive DL, Schwartz LJ. Endometriosis. N Engl J Med1993;328:1759-1769.
2.
2. Lebovic DI, Mueller MD, Taylor RN. Immunobiology of endometriosis. Fertil Steril2001;75:1-10.
3.
3. Sampson J. Peritoneal endometriosis is due to the menstrual dissemination of endometrial tissue into the periotneal cavity. Am J Obstet Gynecol1927;14:422-469.
4.
4. Harada T, Iwabe T, Terakawa N. Role of cytokines in endometriosis. Fertil Steril2001;76:1-10.
5.
5. Bischoff FZ, Simpson JL. Heritability and molecular genetic studies of endometriosis. Hum Reprod Update2000;6:37-44.
7. van der Linden PJ. Theories on the pathogenesis of endometriosis. Hum Reprod1996;11(Suppl 3):53-65.
8.
8. Nothnick WB. Treating endometriosis as an autoimmune disease. Fertil Steril2001;76:223-231.
9.
9. Gazvani MR, Christmas S, Quenby S, Kirwan J, Johnson PM, Kingsland CR. Peritoneal fluid concentrations of interleukin-8 in women with endometriosis: Relationship to stage of disease. Hum Reprod1998;13:1957-1961.
10.
10. Iwabe T, Harada T, Tsudo T, Tanikawa M, Onohara Y, Terakawa N. Pathogenetic significance of incresaed levels of interleukin-8 in the peritoneal fluid of patients with endometriosis. Fertil Steril1998;69:924-930.
11.
11. Punnonen J, Teisala K, Ranta H, Bennett B, Punnonen R. Increased levels of interleukin-6 and interleukin-10 in the peritoneal fluid of patients with endometriosis. Am J Obstet Gynecol1996;174:1522-1526.
12.
12. Bergqvist A, Bruse C, Carlberg M, Carlstrom K. Interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha in endometriotic tissue and in endometrium. Fertil Steril2001;75:489-495.
13.
13. Keenan JA, Chen TT, Chadwell NL, Torry DS, Caudle MR. IL-1 beta, TNF-alpha, and IL-2 in peritoneal fluid and macrophage-conditioned media of women with endometriosis. Am J Reprod Immunol1995;34:381-385.
14.
14. Bazzoni F, Beutler B. The tumor necrosis factor ligand and receptor families. N Engl J Med1996;334:1717-1725.
15.
15. Tabibzadeh S, Satyaswaroop PG, von Wolff M, Strowitzki T. Regulation of TNF-alpha mRNA expression in endometrial cells by TNF-alpha and by oestrogen withdrawal. Mol Hum Reprod1999;5:1141-1149.
16.
16.Laird SM, Tuckerman EM, Saravelos H, Li TC. The production of tumour necrosis factor alpha (TNF-alpha) by human endometrial cells in culture. Hum Reprod1996;11:1318-1323.
17.
17. Overton C, Fernandez-Shaw S, Hicks B, Barlow D, Starkey P. Peritoneal fluid cytokines and the relationship with endometriosis and pain. Hum Reprod1996;11:380-386.
18.
18. Braun DP, Gebel H, House R, Rana N, Dmowski NP. Spontaneous and induced synthesis of cytkines by peripheral blood monocytes in patients with endometriosis. Fertil Steril1996;65:1125-1129.
19.
19. Maas JW, Calhaz-Jorge C, Ter Riet G, Dunselman GA, de Goeij AF, Struijher-Bouolier HA. Tumor necrosis factor-alpha but not interleukin-1 beta or interleukin-8 concentrations correlate with angiogenic activity of peritoneal fluid from patients with minimal to mild endometriosis. Fertil Steril2001;75:180-185.
20.
20. Leibovich SJ, Polverini PJ, Shepard HM, Wiseman DM, Shively V, Nuseir N. Macrophage-induced angiogenesis is mediated by tumour necrosis factor-alpha. Nature1987;329:630-632.
21.
21. Zhang RJ, Wild RA, Ojago JM. Effect of tumor necrosis factor-alpha on adhesion of human endometrial stromal cells to peritoneal mesothelial cells: An in vitro system. Fertil Steril1993;59:1196-1201.
22.
22. Balasch J, Creus M, Fabregues F, et al. Pentoxifylline versus placebo in the treatment of infertility associated with minimal or mild endometriosis: A pilot randomized clinical trial. Hum Reprod1997;12:2046-2050.
23.
23.Wilson AG, di Giovine FS, Blakemore AI, Duff GW. Single base polymorphism in the human tumour necrosis factor alpha (TNF alpha) gene detectable by Ncol restriction of PCR product Hum Mol Genet1992;1:353-353.
24.
24. D'Alfosno D'Alfonso S, Richiardi PM. A polymorphic variation in a putative regulation box of the TNFA promoter region. Immunogenetics1994;39:150-154.
25.
25. Wilson AG, de Vries N, Pociot F, di Giovine FS, van der Putte LB, Duff GW. An allelic polymorphism within the human tumor necrosis factor alpha promoter region is strongly associated with HLA A1, B8, and DR3 alleles. J Exp Med1993;177:557-560.
26.
26. Drouet C, Shakhov AN, Jongeneel CV. Enhancers and transcription factors controlling the inducibility of the tumor necrosis factor-alpha promoter in primary macrophages. J Immunol1991;147:1694-1700.
27.
27. Wilson AG, Symons JA, McDowell TL, McDevitt HO, Duff GW. Effects of a polymorphism in the human tumor necrosis facto alpha promoter on transcriptional activation. Proc Natl Acad Sci U S A1994;94:3195-3199.
28.
28. Kaluza W, Reuss E, Grossmann S, et al. Different transcriptional activity and in vitro TNF-alpha production in psoriasis patients carrying the TNF-alpha 238A promoter polymorphism. J Invest Dermatol2000;114:1180-1183.
29.
29. Revised American Society for Reproductive Medicine classification of endometriosis: 1996. Fertil Steril1997;67:817-821.
30.
30. Fargion S, Valenti L, Dongiovanni P, et al. Tumor necrosis factor alpha promoter polymorphisms influence the phenotypic expression of hereditary hemochromatosis. Blood2001;97:3707-3712.
31.
31. Gonzalez S, Torre-Alonso JC, Martinez-Borra J, et al. TNF-238A promoter polymorphism contributes to susceptibility to ankylosing spondylitis in HLA-B27 negative patients. J Rheumatol2001;28:1288-1293.
32.
32. Koss K, Satsangi J, Fanning GC, Welsh KI, Jewell DP. Cytokine (TNF alpha, LT alpha and IL-10) polymorphisms in inflammatory bowel diseases and normal controls: Differential effects on production and allele frequencies. Genes Immun2000;1:185-190.
33.
33. McGarry F, Walker R, Sturrock R, Field M. The -308.1 polymorphism in the promoter region of the tumor necrosis factor gene is associated with ankylosing spondylitis independent of HLA-B27. J Rheumatol1999;26:1110-1116.
34.
34. Mitchell SA, Grove J, Spurkland A, et al. European Study Group of Primary Sclerosing Cholangitis. Association of the tumour necrosis factor alpha -308 but not the interleukin 10 -627 promoter polymorphism with genetic susceptibility to primary sclerosing cholangitis. Gut2001;49:288-294.
35.
35. van Der Linden MW, van Der Slik AR, Zanelli E, et al. Six microsatellite markers on the short arm of chromosome 6 in relation to HLA-DR3 and TNF-308A in systemic lupus erythematosus. Genes Immun2001;2:373-380.
36.
36. Georgiou I, Syrrou M, Bouba I, et al. Association of estrogen receptor gene polymorphisms with endometriosis. Fertil Steril1999;72:164-166.
37.
37. Baranova H, Canis M, Ivaschenko T, et al. Possible involvement of arylamine N-acetyltransferase 2, glutathione S-transferases M1 and T1 genes in the development of endometriosis. Mol Hum Reprod1999;5:636-641.
38.
38. Baranova H, Bothorishvilli R, Canis M, et al. Glutathione S-transferase M1 gene polymorphism and susceptibility to endometriosis in a French population. Mol Hum Reprod1997;3:775-780.
39.
39. Hadfield RM, Manek S, Weeks DE, Mardon HJ, Barlow DH, Kennedy SH. OXEGENE Collaborative Group. Linkage and association studies of the relationship between endometriosis and genes encoding the detoxification enzymes GSTM1, GSTT1 and CYP1A1. Mol Hum Reprod2001;7:1073-1078.
40.
40. Wieser F, Schneeberger C, Tong D, Tempfer C, Huber JC, Wenzl R. The PROGINS receptor gene polymorphism is associated with endometriosis. Fertil Steril2002;77:309-312.
41.
41. Brinkman BM, Zuijdeest D, Kaijzel EL, Breedveld FC, Verweij CL. Relevance of the tumor necrosis factor alpha (TNF alpha) -308 promoter polymorphism in TNF alpha gene regulation. J Inflamm1995-96;46:32-41.
42.
42. Takashiba S, Shapira L, Amar S, Van Dyke TE. Cloning and characterization of human TNF alpha promoter region. Gene1993;131:307-308.
43.
43. Hamann A, Mantzoros C, Vidal-Puig A, Flier JS. Genetic variability in the TNF-alpha promoter is not associated with type II daibetes mellitus (NIDDM). Biochem Biphys Res Commun1995;211:833-839.
44.
44. Yea SS, Yang YI, Jang WH, Lee YJ, Bae HS, Paik KH. Paik KH. Association between TNF-alpha promoter polymorphism and Helicobacter pylori cagA subtype infection. J Clin Pathol2001;54:703-706.
45.
45. Aidoo M, McElroy PD, Kolczak MS, et al. Tumor necrosis factor-alpha promoter variant 2 (TNF2) is associated with preterm delivery, infant mortality, and malaria morbidity in western Kenya: Asembo Bay Cohort Project IX. Genet Epidemiol2001;21:201-211.
46.
46. Castro J, Telleria JJ, Linares P, Blanco-Quiros A. Increased TNFA*2, but not TNFB*1, allele frequency in Spanish atopic patients. J Investig Allergol Clin Immunol2000;10:149-154.
47.
47. Hohler T, Kruger A, Schneider PM, Schopf RE, Knop J, Rittner C, et al. TNF-alpha promoter polymorphism is associated with juvenile onset psoriasis and psoriatic arthritis. J Invest Dermatol1997;109:562-565.
48.
48. Vanhee D, Gosset P, Boitelle A, Wallaert B, Tonnel AB. Cytokines and cytokins network in silicosis and coal workers' pneumoconiosis. Eur Respir J1995;8:834-842.
