Abstract
To assess the role that polymorphisms of cytokine genes play in genetic predisposition to chronic obstructive pulmonary disease (COPD), the allele and genotype distributions of IL1B, IL1RN, TNFA, LTA, IL6, IL8, and IL10 were studied in COPD patients (N = 319) and healthy individuals (N = 403), residents of Ufa, Bashkortostan. Genotype IL1RN*2/IL1RN*2 of IL1RN was identified as a risk factor for COPD, its frequency being 9.80% in the COPD patients and 4.67% in the healthy subjects (x 2 = 5.45, df = 1, P = 0.02, OR = 2.21). Genotype GG of the LTA polymorphism A252G was significantly more common in the COPD patients than in the controls (7.84% vs. 3.72%; x 2 = 5.00, df = 1, P = 0.026). In patients with COPD stage IV, the frequency of this genotype was twice as high as in those with COPD stages II and III (11.18% vs. 4.79%; x 2 = 3.08, df = 1, P = 0.08). Genotype GG of the TNFA polymorphism G(−308)A in combination with genotype AA of the LTA polymorphism A252G was significantly less frequent in the COPD patients than in the healthy subjects (38.55% vs. 46.93%; x 2 = 8.82, df = 1, P = 0.0039). Genotype GG of the IL6 polymorphism G(−174)C was more frequent in the patients with COPD stage IV (43.75% vs. 31.54% in the patients with COPD stages II and III, x 2 = 4.15, P = 0.042). No significant differences were found between the groups of COPD patients and healthy subjects concerning the genotype frequencies of the polymorphisms T(−511)C and T3953C of IL1B, G(−308)A of TNFA, G(−174)C of IL6, A(−251)C of IL8, and C(−627)A of IL10.
Similar content being viewed by others
References
Genomika-meditsine (Genomics for Medicine). Eds. Ivanov V.I., Kisselev L.L. Moscow: Akademkniga, 2005.
Barnes P.J., Shapiro S.D., Pauwels R.A. 2003. Chronic obstructive pulmonary disease: Molecular and cellular mechanisms. Eur. Respir. J. 22, 672–688.
http://www.goldcopd.com GOLD Workshop Report: Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. Updated 2003.
Agusti A.G.N. 2005. COPD, a multicomponent disease: Implications for management. Respir. Med. 99, 670–682.
Chung K.F. 2001. Cytokines in chronic obstructive pulmonary disease. Eur. Respir. J. 18,suppl. 34, 50–59.
Oudijk E.J., Nijhuis E.H., Zwank M.D., van de Graaf E.A., Mager H.J., Coffer P.J., Lammers J.W., Koenderman L. 2005. Systemic inflammation in COPD visualised by gene profiling in peripheral blood neutrophils. Thorax. 60, 538–544.
Gromova A.Yu., Simbirtsev A.S. 2005. Polymorphism of human genes of the IL-1 family. Tsitokiny Vospal. 4, 3–12.
Seifart C., Dempfle A., Plagens A., Seifart U., Clostermann U., Muller B., Vogelmeier C., von Wichert P. 2005. TNF-α-, TNF-β-, IL-6-, and IL-10-promoter polymorphisms in patients with chronic obstructive pulmonary disease. Tissue Antigens. 65, 93–100.
Ferrarotti I., Zorzetto M., Beccaria M., Gile L.S., Porta R., Ambrosino N., Pignatti P.F., Cerveri I., Pozzi E., Luisetti M. 2003. Tumour necrosis factor family genes in a phenotype of COPD associated with emphysema. Eur. Respir. J. 21, 444–449.
Hull J., Ackerman H., Isles K., Usen S., Pinder M., Thomson A., Kwiatkowski D. 2001. Unusual haplotypic structure of IL8, a susceptibility locus for a common respiratory virus. Am. J. Hum. Genet. 69, 413–419.
Kucukaycan M., van Krugten M., Pennings H.-J., Huizinga T.W.J., Buurman W.A., Dentener M.A. Wouters E.F.M. 2002. Tumor Necrosis Factor-α +489G/A gene polymorphism is associated with chronic obstructive pulmonary disease. Respir. Res. 3, 29–46.
Cipriano C., Caruso C., Lio D., Giacconi R., Malavolta M., Muti E., Gasparini N., Franceschi C., Mocchegiani E. 2005. The −308G/A polymorphism of TNF-α influences immunological parameters in old subjects affected by infectious diseases. Int. J. Immunogenet. 32, 13–18.
Broekhuizen R., Grimble R.F., Howell W.M., Shale D.J., Creutzberg E.C., Wouters E.F., Schols A.M. 2005. Pulmonary cachexia, systemic inflammatory profile, and the interleukin 1β −511 single nucleotide polymorphism. Am. J. Clin. Nutr. 82, 1059–1064.
Hu R.C., Xu Y.J., Zhang Z.X., Xie J.G. 2003. Polymorphism of interleukin-10 gene promoter and its association with susceptibility to chronic obstructive pulmonary disease in Chinese Han people. Zhonghua Yi Xue Yi Chuan Xue Za Zi. 20, 504–507.
Grove J., Daly A.K., Bassendine M.F., Gilvarry E., Day C.P. 2000. Interleukin 10 promoter region polymorphisms and susceptibility to advanced alcoholic liver disease. Gut. 46, 540–545.
Fishman D., Faulds G., Jeffery R., Mohamed-Ali V., Yudkin J.S., Humphries S., 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. Clin. Invest. 102, 1369–1376.
Chen W.C., Wu H.C., Chen H.Y., Wu M.C., Hsu C.D., Tsai F.J. 2001. Interleukin-1β gene and receptor antagonist gene polymorphisms in patients with calcium oxalate stones. Urol. Res. 29, 321–324.
Hurme M., Santtila S. 1998. IL-1 receptor antagonist (IL-1RA) plasma levels are co-ordinately regulated by both IL-1RA and IL-1β genes. Eur. J. Immunol. 28, 2598–2602
Joos L., McIntyre L., Ruan J., Connett J.E., Anthonisen N.R., Weir T.D., Pare P.D., Sandford A.J. 2001. Association of IL-1beta and IL-1 receptor antagonist haplotypes with rate of decline in lung function in smokers. Thorax. 56, 863–866.
Karjalainen J., Hulkkonen J., Hurme M. 2002. IL-1 haplotypes and lung function decline. Thorax. 57, 561–562.
Warzocha K., Ribeiro P., Bienvenu J., et al. 1998. Genetic polymorphisms in the tumor necrosis factor locus influence non-Hodgkin’s lymphoma outcome. Blood. 91, 3574–3581.
Roitt I., Brostoff J., Mail D. 2000. Immunology [Russian translation]. Moscow: Mir.
Wilson A.G., Symon J.A., McDowel T.L., et al. 1997. Effects of a polymorphism in the human tumor necrosis factor α promoter on transcriptional activation. Proc. Natl. Acad. Sci. USA. 94, 3195–3199.
Huang S.L., Su C.H., Chang S.C. 1997. Tumor necrosis factor-α gene polymorphism in chronic bronchitis. Am. J. Respir. Crit. Care Med. 156, 1436–1439.
Swofford L., Selander B. 1997. BIOSYS-2: Computer Program for the Analysis of Allelic Variation in Genetics. Department of Genetics and Development, University of Illinois.
Xie X., Ott J. 1993. Testing linkage disequilibrium between a disease gene and marker loci. Am. J. Hum. Genet. 53, 1107.
Glanz S.A. 1998. BIOSTATISTICA, Primer of biostatistics version 4.03. McGrow Hill.
www.statistica.com. StatSoft Inc., USA. Statistica v.6.0.
Messer G., Spengler U., Jung M.C. 1991. Polymorphic structure of the tumor necrosis factor (TNF) locus: An NcoI polymorphism in the first intron of the human TNF-β gene correlates with a variant amino acid in position 26 and a reduced level of TNF-β production. J. Exp. Med. 173, 209.
Author information
Authors and Affiliations
Additional information
Original Russian Text © K.V. Danilko, G.F. Korytyna, L.Z. Akhmadishina, D.G. Yanbaeva, Sh.Z. Zagidullin, T.V. Victorova, 2007, published in Molekulyarnaya Biologiya, 2007, Vol. 41, No. 1, pp. 26–36.
Rights and permissions
About this article
Cite this article
Danilko, K.V., Korytyna, G.F., Akhmadishina, L.Z. et al. Association of polymorphisms of cytokine genes (IL1B, IL1RN, TNFA, LTA, IL6, IL8, and IL10) with chronic obstructive pulmonary disease. Mol Biol 41, 22–31 (2007). https://doi.org/10.1134/S0026893307010049
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1134/S0026893307010049