Association of a functional 17β-estradiol sensitive IL6-174G/C promoter polymorphism with early-onset type 1 diabetes in females

Human Molecular Genetics

Volumn 12, Issue 10, 2003, Pages 1101-1110

  Kristiansen, Ole P ^a   Nolsøe, Runa L ^a   Larsen, Lykke ^a   Gjesing, Anette M P ^a   Johannesen, Jesper ^a   Larsen, Zenia M ^a   Lykkesfeldt, Anne E ^b   Karlsen, Allan E ^a   Pociot, Flemming ^a   Mandrup Poulsen, Thomas ^a,c  

^a STENO DIABETES CENTER   (Denmark)

^b DANISH CANCER SOCIETY RESEARCH CENTER   (Denmark)

^c KAROLINSKA INSTITUTE   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

ESTRADIOL; INTERLEUKIN 6;

ARTICLE; CONTROLLED STUDY; DENMARK; DISEASE PREDISPOSITION; ESTROGEN ACTIVITY; FEMALE; GENE SEGREGATION; GENETIC LINKAGE; GENETIC SUSCEPTIBILITY; GENETIC VARIABILITY; GENOTYPE; HERITABILITY; HUMAN; INSULIN DEPENDENT DIABETES MELLITUS; MAJOR CLINICAL STUDY; MALE; MEIOSIS; MOUSE; NONHUMAN; NUCLEOTIDE SEQUENCE; ONSET AGE; PRIORITY JOURNAL; PROGENY; SEX DIFFERENCE; SINGLE NUCLEOTIDE POLYMORPHISM; ANIMAL; GENETIC POLYMORPHISM; GENETICS; METABOLISM; PROMOTER REGION;

AGE OF ONSET; ANIMALS; DIABETES MELLITUS, TYPE 1; ESTRADIOL; FEMALE; HUMANS; INTERLEUKIN-6; MALE; MICE; POLYMORPHISM, GENETIC; PROMOTER REGIONS (GENETICS); SEX FACTORS;

EID: 0038440550     PISSN: 09646906     EISSN: None     Source Type: Journal    
DOI: 10.1093/hmg/ddg132     Document Type: Article

References (52)

1. Davies, J.L., Kawaguchi, Y., Bennett, S.T., Copeman, J.B., Cordell, H.J., Pritchard, L.E., Reed, P.W., Gough, S.C., Jenkins, S.C., Palmer, S.M. et al. (1994) A genome-wide search for human type 1 diabetes susceptibility genes. Nature, 371, 130-136.
2. Hashimoto, L., Habita, C., Beressi, J.P., Delepine, M., Besse, C., Cambon-Thomsen, A., Deschamps, I., Rotter, J.I., Dioulah, S., James, M.R. et al. (1994) Genetic mapping of a susceptibility locus for insulin-dependent diabetes mellitus on chromosome 11q. Nature, 371, 161-164.
3. Mein, C.A., Esposito, L., Dunn, M.G., Johnson, G.C., Timms, A.E., Goy, J.V., Smith, A.N., Sebag-Montefiore, L., Merriman, M.E., Wilson, A.J. et al. (1998) A search for type 1 diabetes susceptibility genes in families from the United Kingdom. Nat. Genet., 19, 297-300.
4. Concannon, P., Gogolin-Ewens, K.J., Hinds, D.A., Wapelhorst, B., Morrison, V.A., Stirling, B., Mitra, M., Farmer, J., Williams, S.R., Cox, N.J. et al. (1998) A second-generation screen of the human genome for susceptibility to insulin-dependent diabetes mellitus. Nat. Genet., 19, 292-296.
5. Nerup, J., Pociot, F. and European Consortium for IDDM Studies (2001) A genomewide scan for type 1-diabetes susceptibility in Scandinavian families: identification of new loci with evidence of interactions. Am. J. Hum. Genet., 69, 1301-1313.
6. Cox, N.J., Wapelhorst, B., Morrison, V.A., Johnson, L., Pinchuk, L., Spielman, R.S., Todd, J.A. and Concannon, P. (2001) Seven regions of the genome show evidence of linkage to type 1 diabetes in a consensus analysis of 767 multiplex families. Am. J. Hum. Genet., 69, 820-830.
7. Kamradt, T. and Mitchison, N.A. (2001) Tolerance and autoimmunity. New Engl. J. Med., 344, 655-664.
8. Akira, S., Taga, T and Kishimoto, T. (1993) Interleukin-6 in biology and medicine. Adv. Immunol., 54, 1-78.
9. Baumann, H. and Gauldie, J. (1994) The acute phase response. Immunol. Today, 15, 74-80.
10. Wilder, R.L. (1995) Neuroendocrine-immune system interactions and autoimmunity. A. Rev. Immunol., 13, 307-338.
11. Lotz, M. and Guerne, P.A. (1991) Interleukin-6 induces the synthesis of tissue inhibitor of metalloproteinases-1/erythroid potentiating activity (TIMP-1/EPA). J. Biol. Chem., 266, 2017-2020.
12. Tilg, H., Trehu, E., Atkins, M.B., Dinarello, C.A. and Mier, J.W. (1994) Interleukin-6 (IL-6) as an anti-inflammatory cytokine: induction of circulating IL-1 receptor antagonist and soluble tumor necrosis factor receptor p55. Blood, 83, 113-118.
13. Romano, M., Sironi, M., Toniatti, C., Polentarutti, N., Fruscella, P., Ghezzi, P, Faggioni, R., Luini, W., van, Hinsberg, V., Sozzani, S. et al. (1997) Role of IL-6 and its soluble receptor in induction of chemokines and leukocyte recruitment. Immunity, 6, 315-325.
14. Ishihara, K. and Hirano, T. (2002) IL-6 in autoimmune disease and chronic inflammatory proliferative disease. Cytokine Growth Factor Rev., 13, 357.
15. Tchorzewski, H., Glowacka, E., Banasik, M., Lewkowicz, P. and Szalapska-Zawodniak, M. (2001) Activated T lymphocytes from patients with high risk of type I diabetes mellitus have different ability to produce interferon-gamma, interleukin-6 and interleukin-10 and undergo anti-CD95 induced apoptosis after insulin stimulation. Immunol. Lett., 75, 225-234.
16. Kovalovich, K., Li, W, DeAngelis, R., Greenbaum, L.E., Ciliberto, G. and Taub, R. (2001) Interleukin-6 protects against Fas-mediated death by establishing a critical level of anti-apoptotic hepatic proteins FLIP, Bcl-2, and Bcl-xL. J. Biol. Chem., 276, 26605-26613.
17. Campbell, I.L., Cutri, A., Wilson, A. and Harrison, L.C. (1989) Evidence for IL-6 production by and effects on the pancreatic beta-cell. J. Immunol., 143, 1188-1191.
18. DiCosmo, B.F., Picarella, D. and Flavell, R.A. (1994) Local production of human IL-6 promotes insulitis but retards the onset of insulin-dependent diabetes mellitus in non-obese diabetic mice. Int. Immunol., 6, 1829-1837.
19. Campbell, I.L., Hobbs, M.V., Dockter, J., Oldstone, M.B. and Allison, J. (1994) Islet inflammation and hyperplasia induced by the pancreatic islet-specific overexpression of interleukin-6 in transgenic mice. Am. J. Pathol., 145, 157-166.
20. Suematsu, S., Matsusaka, T., Matsuda, T., Ohno, S., Miyazaki, J., Yamamura, K., Hirano, T. and Kishimoto, T. (1992) Generation of plasmacytomas with the chromosomal translocation t(12;15) in interleukin 6 transgenic mice. Proc. Natl Acad. Sci. USA, 89, 232-235.
21. Fattori, E., Della, R.C., Costa, P., Giorgio, M., Dente, B., Pozzi, L. and Ciliberto, G. (1994) Development of progressive kidney damage and myeloma kidney in interleukin-6 transgenic mice. Blood, 83, 2570-2579.
22. Woodroofe, C., Muller, W. and Ruther, U. (1992) Long-term consequences of interleukin-6 overexpression in transgenic mice. DNA Cell. Biol., 11, 587-592.
23. Bowcock, A.M., Kidd, J.R., Lathrop, G.M., Daneshvar, L., May, L.T., Ray, A., Sehgal, P.B., Kidd, K.K. and Cavalli-Sforza, L.L. (1988) The human 'interferon-beta 2/hepatocyte stimulating factor/interleukin-6' gene: DNA polymorphism studies and localization to chromosome 7p21. Genomics, 3, 8-16.
24. Mock, B.A., Nordan, R.P., Justice, M.J., Kozak, C., Jenkins, N.A., Copeland, N.G., Clark, S.C., Wong, G.G. and Rudikoff, S. (1989) The murine II-6 gene maps to the proximal region of chromosome 5. J. Immunol., 142, 1372-1376.
25. McAleer, M.A., Reifsnyder, P., Palmer, S.M., Prochazka, M., Love, J.M., Copeman, J.B., Powell, E.E., Rodrigues, N.R., Prins, J.B., Serreze, D.V. et al. (1995) Crosses of NOD mice with the related NON strain. A polygenic model for IDDM. Diabetes, 44, 1186-1195.
26. Paterson, A.D. and Petronis, A. (1999) Sex of affected sibpairs and genetic linkage to type 1 diabetes. Am. J. Med. Genet., 84, 15-19.
27. Jahromi, M.M., Millward, B.A. and Demaine, A.G. (2000) A polymorphism in the promoter region of the gene for interleukin-6 is associated with susceptibility to type 1 diabetes mellitus. J. Interferon Cytokine Res., 20, 885-888.
28. Fishman, D., Faulds, G., Jeffery, R., Mohamed-Ali, V., Yudkin, J.S., Humphries, S. and Woo, P. (1998) The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J. Clin. Invest., 102, 1369-1376.
29. Hulkkonen, J., Pertovaara, M., Antonen, J., Pasternack, A. and Hurme, M. (2001) Elevated interleukin-6 plasma levels are regulated by the promoter region polymorphism of the IL6 gene in primary Sjogren's syndrome and correlate with the clinical manifestations of the disease. Rheumatology (Oxford), 40, 656-661.
30. Burzotta, F., Iacoviello, L., Di Castelnuovo, A., Glieca, F., Luciani, N., Zamparelli, R., Schiavello, R., Donati, M.B., Maseri, A., Possati, G. et al. (2001) Relation of the - 174 G/C polymorphism of interleukin-6 to interleukin-6 plasma levels and to length of hospitalization after surgical coronary revascularization. Am. J. Cardiol., 88, 1125-1128.
31. Kilpinen, S., Hulkkonen, J., Wang, X.Y. and Hurme, M. (2001) The promoter polymorphism of the interleukin-6 gene regulates interleukin-6 production in neonates but not in adults. Eur Cytokine New, 12, 62-68.
32. Terry, C.F., Loukaci, V. and Green, F.R. (2000) Cooperative influence of genetic polymorphisms on interleukin 6 transcriptional regulation. J. Biol. Chem., 275, 18138-18144.
33. Pascual, M., Nieto, A., Mataran, L., Balsa, A., Pascual-Salcedo, D. and Martin, J. (2000) IL-6 promoter polymorphisms in rheumatoid arthritis. Genes Immun., 1, 338-340.
34. Veres, A., Prohaszka, Z., Kilpinen, S., Singh, M., Fust, G. and Hurme, M. (2002) The promoter polymorphism of the IL-6 gene is associated with levels of antibodies to 60-kDa heat-shock proteins. Immunogenetics, 53, 851-856.
35. Bazrafshani, M.R., Hajeer, A.H., Ollier, W.E. and Thornhill, M.H. (2002) IL-1B and IL-6 gene polymorphisms encode significant risk for the development of recurrent aphthous stomatitis (RAS). Genes. Immun., 3, 302-305.
36. Pottratz, S.T., Bellido, T., Mocharla, H., Crabb, D. and Manolagas, S.C. (1994) 17 beta-Estradiol inhibits expression of human interleukin-6 promoter-reporter constructs by a receptor-dependent mechanism. J. Clin. Invest., 93, 944-950.
37. Ray, P., Ghosh, S.K., Zhang, D.H. and Ray, A. (1997) Repression of interleukin-6 gene expression by 17 beta-estradiol: inhibition of the DNA-binding activity of the transcription factors NF-IL6 and NF-kappa B by the estrogen receptor. FEBS Lett., 409, 79-85.
38. Papassotiropoulos, A., Bagli, M., Jessen, F., Bayer, T.A., Maier, W., Rao, M.L. and Heun, R. (1999) A genetic variation of the inflammatory cytokine interleukin-6 delays the initial onset and reduces the risk for sporadic Alzheimer's disease. Ann. Neurol., 45, 666-668.
39. Ewens, W.J. and Spielman, R.S. (1995) The transmission/disequilibrium test: history, subdivision, and admixture. Am. J. Hum. Genet., 57, 455-464.
40. Risch, N. and Merikangas, K. (1996) The future of genetic studies of complex human diseases. Science, 273, 1516-1517.
41. Cucca, F., Goy, J.V., Kawaguchi, Y., Esposito, L., Merriman, M.E., Wilson, A.J., Cordell, H.J., Bain, S.C. and Todd, J.A. (1998) A male-female bias in type 1 diabetes and linkage to chromosome Xp in MHC HLA-DR3-positive patients. Nat. Genet., 19, 301-302.
42. Delepine, M., Pociot, F., Habita, C., Hashimoto, L., Froguel, P., Rotter, J., Cambon-Thomsen, A., Deschamps, I., Djoulah, S., Weissenbach, J. et al. (1997) Evidence of a non-MHC susceptibility locus in type 1 diabetes linked to HLA on chromosome 6. Am. J. Hum. Genet., 60, 174-187.
43. Jordanides, N., Eskdale, J., Stuart, R. and Gallagher, G. (2000) Allele associations reveal four prominent haplotypes at the human interleukin-6 (IL-6) locus. Genes. Immun., 1, 451-455.
44. Galien, R., Evans, H.F. and Garcia, T. (1996) Involvement of CCAAT/enhancer-binding protein and nuclear factor-kappa B binding sites in interleukin-6 promoter inhibition by estrogens. Mol. Endocrinol., 10, 713-722.
45. Stein, B. and Yang, M.X. (1995) Repression of the interleukin-6 promoter by estrogen receptor is mediated by NF-kappa B and C/EBP beta. Mol. Cell. Biol., 15, 4971-4979.
46. Costanzo, C., Piacentini, G., Vicentini, L., Armenante, F., Mazzi, P., Savio, C., Faggioli, L., Boner, A. and Palmieri, M. (1999) Cell-specific differences in the regulation of IL-6 expression by PMA. Biochem. Biophys. Res. Commun., 260, 577-581.
47. Tanabe, O., Akira, S., Kamiya, T., Wong, G.G., Hirano, T. and Kishimoto, T. (1988) Genomic structure of the murine IL-6 gene. High degree conservation of potential regulatory sequences between mouse and human. J. Immunol., 141, 3875-3881.
48. Makino, S., Kunimoto, K., Muraoka, Y. and Katagiri, K. (1981) Effect of castration on the appearance of diabetes in NOD mouse. Jikken Dobutsu, 30, 137-140.
49. Ohlsson, H., Lykkesfeldt, A.E., Madsen, M.W. and Briand, P. (1998) The estrogen receptor variant lacking exon 5 has dominant negative activity in the human breast epithelial cell line HMT-3522S1. Cancer Res., 58, 4264-4268.
50. Spielman, R.S. and Ewens, W.J. (1998) A sibship test for linkage in the presence of association: the sib transmission/disequilibrium test. Am. J. Hum. Genet., 62, 450-458.
51. Lie, B.A., Todd, J.A., Pociot, F., Nerup, J., Akselsen, H.E., Joner, G., Dahl-Jorgensen, K., Ronningen, K.S., Thorsby, E. and Undlien, D.E. (1999) The predisposition to type 1 diabetes linked to the human leukocyte antigen complex includes at least one non-class II gene. Am. J. Hum. Genet., 64, 793-800.
52. Larsen, Z.M., Kristiansen, O.P., Mato, E., Johannesen, J., Puig-Domingo, M., de-Leiva, A., Nerup, J. and Pociot, F. (1999) IDDM12 (CTLA4) on 2q33 and IDDM13 on 2q34 in genetic susceptibility to type 1 diabetes (insulin-dependent). Autoimmunity, 31, 35-42.