Abstract
Endometriosis is regarded as a complex trait, in which genetic and environmental factors contribute to the disease phenotype. We investigated whether the interleukin (IL) 1beta (+3953) polymorphism is associated with the severity of endometriosis. Diagnosis of endometriosis was made on the basis of laparoscopic findings. Stage of endometriosis was determined according to the Revised American Fertility Society classification. 118 women were enrolled in the study. 78 women didnot have endometriosis, 6 women had stage I, 3 had stage II, 13 had stage III and 18 had stage IV endometriosis. Polymerase Chain Reaction (PCR), Restriction Fragment Length Polymorphism (RFLP), and agarose gel electrophoresis techniques were used to determine the IL 1beta (+3953) genotype. Frequencies of the IL-1beta (+3953) genotypes in the control group were: CC, 0.397; TT, 0.115; CT, 0.487. Frequencies of the IL-1beta (+3953) genotypes in cases were: CC, 0.375; TT, 0.225; CT, 0.400. We found a 2.22 fold increase in TT genotype in the endometriosis group. However, the difference was not statistically significant (P > 0.05). We also observed an increase in the frequency of IL-1beta (+3953) T allele in the endometriosis group. However, the difference was not statistically significant. We also investigated the association between IL-1beta (+3953) polymorphism and the severity of endometriosis. The frequencies of CC+CT genotypes in stage I, III and IV endometriosis patients were 83.3, 84/6 and 72.2%, respectively; and TT genotypes were 16.7, 15.4 and 27.8%, respectively. We observed a statistically insignificant increase in TT genotype in stage IV endometriosis (P > 0.05). We suggest that IL-1beta (+3953) polymorphism is not associated with endometriosis in Turkish women.
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References
D’Amora P, Sato H, Giraõ MJBC, Silva IDCG, Schor E (2006) Polymorphisms in exons 1B and 1C of the type I interleukin-1 receptor gene in patients with endometriosis. Am J Reprod Immunol 56:178–184
Kitawaki J, Kiyomizu M, Obayashi H, Ohta M, Ishihara H, Hasegawa G et al (2006) Synergistic effect of interleukin-6 promoter (IL6–634C/G) and intercellular adhesion molecule-1 (ICAM-1 469 K/E) gene polymorphisms on the risk of endometriosis in Japanese women. Am J Reprod Immunol 56:267–274
Sampson JA (1927) Peritoneal endometriosis due to the menstrual dissemination of endometrial tissue into the peritoneal cavity. Am J Obstet Gynecol 14:422–469
Houston DE, Noller KL, Melton LJ 3rd et al (1987) Incidence of pelvic endometriosis in Rochester, Minnesota, 1970–1979. Am J Epidemiol 125:959–969
Kjerulff KH, Erickson BA, Langenberg PW (1996) Chronic gynecological conditions reported by US women: findings from the National Health Interview Survey, 1984 to 1992. Am J Public Health 86:195–199
Zondervan KT, Cardon LR, Kennedy SH (2001) The genetic basis of endometriosis. Curr Opin Obstet Gynecol 3:309–314
Zhang X, Hei P, Deng L, Lin J (2007) Interleukin-10 gene promoter polymorphisms and their protein production in peritoneal fluid in patients with endometriosis. Mol Hum Reprod 13(2):135–140
Lin J, Zhang X, Qian Y, Ye Y, Shi Y, Xu K et al (2003) Glutathione S-transferase m1 and t1 genotypes and endometriosis risk: a case-controlled study. Chin Med J (Engl) 116:777–780
Hsieh YY, Chang CC, Tsai FJ, Peng CT, Yeh LS, Lin CC (2005) Polymorphism for transforming growth factor beta 1-509 (TGF-b1–509): association with endometriosis. Biochem Genet 43:203–210
Luisi S, Galleri L, Marini F, Ambrosini G, Brandi ML, Petraglia F (2006) Estrogen receptor gene polymorphisms are associated with recurrence of endometriosis. Fertil Steril 85:764–766
Seli E, Arici A (2003) Endometriosis: interaction of immune and endocrine systems. Semin Reprod Med 21(2):135–144
Iwabe T, Harada T, Terakawa N (2002) Role of cytokines in endometriosis-associated infertility. Gynecol Obstet Invest 53:19–25
Wu MY, Ho HN (2003) The role of cytokines in endometriosis. Am J Reprod Immunol 49:285–296
Di Giovine FS, Takhsh E, Blakemore AI, Duff GW (1992) Single base polymorphism at 511 in the human interleukin-1b gene (IL1b). Hum Mol Genet 1:450
Pociot F, Molvig J, Wogensen L, Worsaae H, Nerup J (1992) A Taq polymorphism in the human interleukin-1b (IL-1b) gene correlates with IL-1b secretion in vitro. Eur J Clin Invest 22:396–402
Wang CY, Shen YC, Su CH, Lo FY, Lee SH, Tsai HY, Fan SS (2007) Investigation of the association between interleukin-1β polymorphism and normal tension glaucoma. Mol Vis 13:719–723
Lebovic DI, Bentzien F, Chao VA, Garrett EN, Meng YG, Taylor RN (2000) Induction of an angiogenic phenotype in endometriotic stromal cell cultures by interleukin-1b. Mol Hum Reprod 6:269–275
Viganò P, Gaffuri B, Somigliana E, Busacca M, Di Blasio AM, Vignali M (1998) Expression of intercellular adhesion molecule (ICAM)-1 mRNA and protein is enhanced in endometriosis versus endometrial stromal cells in culture. Mol Hum Reprod 4:1150–1156
Lebovic DI, Chao VA, Taylor RN (2004) Peritoneal macrophages induce RANTES (regulated on activation, normal T cell expressed and secreted) chemokine gene transcription in endometrial stromal cells. J Clin Endocrinol Metab 89:1397–1401
Lebovic DI, Chao VA, Martini JF, Taylor RN (2001) IL-1b induction of RANTES (regulated upon activation, normal T cell expressed and secreted) chemokine gene expression in endometriotic stromal cells depends on a nuclear factor-B site in the proximal promoter. J Clin Endocrinol Metab 86:4759–4764
Akoum A, Lemay A, Maheux R (2002) Estradiol and interleukin-1b exert a synergistic stimulatory effect on the expression of the chemokine regulated upon activation, normal T cell expressed, and secreted in endometriotic cells. J Clin Endocrinol Metab 87:5785–5792
Khorram O, Taylor RN, Ryan IP, Schall TJ, Landers DV (1993) Peritoneal fluid concentrations of the cytokine RANTES correlate with the severity of endometriosis. Am J Obstet Gynecol 169:1545–1549
Revised American Society for Reproductive Medicine classification of endometriosis: 1996 (1997) Fertil Steril 67(5):817–821
Miller SA, Dykes DD, Polesky HS (1988) Simples salting out procedure for extracting DNA from human nucleated cells. Nucleic Acid Res 16/3:1215
Treszl A, Toth-Heyn P, Kocsis I, Nobilis A, Schuler A, Tulassay T et al (2002) Interleukin genetic variants and the risk of renal failure in infants with infection. Pediatr Nephrol 17:713–717
Gupta S, Goldberg JM, Aziz N, Goldberg E, Krajcir N, Agarwal A (2008) Pathogenic mechanisms in endometriosis-associated infertility. Fertil Steril 90(2):247–257
Lachapelle MH, Hemmings R, Roy DC, Falcone T, Miron P (1996) Flow cytometric evaluation of leukocyte subpopulations in the follicular fluids of infertile patients. Fertil Steril 65:1135–1140
Pellicer A, Albert C, Mercader A, Bonilla-Musoles F, Remohi J, Simon C (1998) The follicular and endocrine environment in women with endometriosis: local and systemic cytokine production. Fertil Steril 70:425–431
Garrido N, Navarro J, Remohi J, Simon C, Pellicer A (2000) Follicular hormonal environment and embryo quality in women with endometriosis. Hum Reprod Update 6:67–74
Wunder DM, Mueller MD, Birkhauser MH, Bersinger NA (2006) Increased ENA-78 in the follicular fluid of patients with endometriosis. Acta Obstet Gynecol Scand 85:336–342
Rogus J, Beck JD, Offenbacher S, Huttner K, Iacoviello L, Latella MC et al (2008) IL1B gene promoter haplotype pairs predict clinical levels of interleukin-1beta and C-reactive protein. Hum Genet 123(4):387–398
Singh H, Sachan R, Goel H, Mittal B (2008) Genetic variants of interleukin-1RN and interleukin-1b genes and risk of cervical cancer. BJOG 115:633–638
Dinarello CA (1996) Biologic basis for interleukin-1 in disease. Blood 87:2095–2147
Arend WP, Malyak M, Guthridge CJ, Gabay C (1998) Interleukin-1 receptor antagonist: role in biology. Annu Rev Immunol 16:27–55
Dinarello CA (1998) Interleukin-1, interleukin-1 receptors and interleukin-1 receptor antagonist. Int Rev Immunol 16:457–499
Hsieh YY, Chang CC, Tsai FJ, Wu JY, Shi YR, Tsai HD, Tsai CH (2001) Polymorphisms for interleukin-1 beta (IL-1 beta)-511 promoter, IL-1 beta exon 5, and IL-1 receptor antagonist: nonassociation with endometriosis. J Assist Reprod Genet 18:506–511
Hsieh YY, Chang CC, Tsai FJ, Hsu Y, Tsai HD, Tsai CH (2002) Polymorphisms for interleukin 4 (IL-4) -590 promoter, IL-4 intron3, and tumor necrosis factor alpha -308 promoter: non association with endometriosis. J Clin Lab Anal 16:121–126
Hsieh YY, Chang CC, Tsai FJ, Hsu CM, Lin CC, Tsai CH (2005) Interleukin-2 receptor beta (IL-2R beta)-627*C homozygote but not IL-12R beta 1 codon 378 or IL-18 105 polymorphism is associated with higher susceptibility to endometriosis. Fertil Steril 84:510–512
Lee MK, Park AJ, Kim DH (2002) Tumor necrosis factor-alpha and interleukin-6 promoter gene polymorphisms are not associated with an increased risk of endometriosis. Fertil Steril 77:1304–1305
Wieser F, Fabjani G, Tempfer C, Schneeberger C, Sator M, Huber J, Wenzl R (2003) Analysis of an interleukin-6 gene promoter polymorphism in women with endometriosis by pyrosequencing. J Soc Gynecol Investig 10:32–36
Wieser F, Hefler L, Tempfer C, Vlach U, Schneeberger C, Huber J, Wenzl R (2003) Polymorphism of the interleukin-1beta gene and endometriosis. J Soc Gynecol Investig 10:172–175
Bhanoori M, Babu KA, Deenadayal M, Kennedy S, Shivaji S (2005) The interleukin-6–174 G/C promoter polymorphism is not associated with endometriosis in South Indian women. J Soc Gynecol Investig 12:365–369
Wen J, Deng L, Zhang XM (2006) Research on relationship between gene polymorphisms of interleukin-1 family and endometriosis. Zhejiang Da Xue Xue Bao Yi Xue Ban 35:653–657
Kang S, Kim JW, Park NH, Song YS, Park SY, Kang SB et al (2007) Interleukin- 1 beta-511 polymorphism and risk of cervical cancer. J Korean Med Sci 22:110–113
McLaren J, Prentice A, Charnock-Jones DS et al (1996) Vascular endothelial growth factor is produced by peritoneal fluid macrophages in endometriosis and is regulated by ovarian steroids. J Clin Invest 98:482–489
Laird SM, Tuckerman EM, Saravelos H, Li TC (1996) The production of tumour necrosis factor alpha (TNF-alpha) by human endometrial cells in culture. Hum Reprod 11:1318–1323
Eisermann J, Gast MJ, Pineda J, Odem RR, Collins JL (1988) Tumor necrosis factor in peritoneal fluid of women undergoing laparoscopic surgery. Fertil Steril 50:573–579
Akoum A, Lemay A, Brunet C et al (1995) Secretion of monocyte chemotactic protein-1 by cytokine-stimulated endometrial cells of women with endometriosis. Le groupe d’investigation en gynecologie. Fertil Steril 63:322–328
Akoum A, Lemay A, Brunet C et al (1995) Cytokine-induced secretion of monocyte chemotactic protein-1 by human endometriotic cells in culture. Am J Obstet Gynecol 172:594–600
Taketani Y, Kuo TM, Mizuno M (1992) Comparison of cytokine levels and embryo toxicity in peritoneal fluid in infertile women with untreated or treated endometriosis. Am J Obstet Gynecol 167:265–270
Arici A, Oral E, Attar E et al (1997) Monocyte chemotactic protein-1 concentration in peritoneal fluid of women with endometriosis and its modulation of expression in mesothelial cells. Fertil Steril 67:1065–1072
Gupta S, Goldberg JM, Aziz N, Goldberg E, Krajcir N, Agarwal A (2008) Pathogenic mechanisms in endometriosis-associated infertility. Fertil Steril 90(2):247–257
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Attar, R., Agachan, B., Kucukhuseyin, O. et al. Association of interleukin 1beta gene (+3953) polymorphism and severity of endometriosis in Turkish women. Mol Biol Rep 37, 369–374 (2010). https://doi.org/10.1007/s11033-009-9800-3
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DOI: https://doi.org/10.1007/s11033-009-9800-3