Skip to main content
Erschienen in: European Journal of Clinical Microbiology & Infectious Diseases 10/2010

01.10.2010 | Brief Report

Association of genetic polymorphisms in the IL12-IFNG pathway with susceptibility to and prognosis of pulmonary tuberculosis in a Chinese population

verfasst von: J. Wang, S. Tang, H. Shen

Erschienen in: European Journal of Clinical Microbiology & Infectious Diseases | Ausgabe 10/2010

Einloggen, um Zugang zu erhalten

Abstract

Cytokines are crucial in activation of the cell-mediated immunity required for eliminating pathogens and controlling intracellular growth of Mycobacterium tuberculosis (TB). Genetic variants in the IL12-IFNG axis are hypothesized to be involved in the development and progression of TB. Genetic polymorphisms of rs2243115 and rs568408 in IL12A, rs3212227 in IL12B and rs2430561 in IFNG(+874) were detected in 522 pulmonary TB cases and 527 controls recruited from Yangzhong and Wujin County of China. It was found that genetic variants TG/GG of rs2243115(IL12A) were associated with a decreased risk of TB, with odds ratio (95% confidence interval) of 0.70 (0.49–0.99), whereas variant genotypes AT/TT of rs2430561(IFNG) conferred 82% less risk for treatment failure, with a hazard ratio of 0.18 (95% confidence interval 0.04–0.73). Cumulative effects analysis revealed that the risk of TB increased significantly with the number of unfavorable genotypes in IL12 genes. Furthermore, MDR analysis showed potential higher-order gene–gene and gene–environment interactions and indicated different outcomes based on distinct genotype profiles. Results from this study demonstrate that genetic polymorphisms of the IL12-IFNG pathway may individually or jointly contribute to the susceptibility to and prognosis of pulmonary TB.
Literatur
1.
Zurück zum Zitat Young DB, Perkins MD, Duncan K, Barry CE 3rd (2008) Confronting the scientific obstacles to global control of tuberculosis. J Clin Invest 118(4):1255–1265CrossRefPubMed Young DB, Perkins MD, Duncan K, Barry CE 3rd (2008) Confronting the scientific obstacles to global control of tuberculosis. J Clin Invest 118(4):1255–1265CrossRefPubMed
2.
Zurück zum Zitat Bellamy R (2003) Susceptibility to mycobacterial infections: the importance of host genetics. Genes Immun 4(1):4–11CrossRefPubMed Bellamy R (2003) Susceptibility to mycobacterial infections: the importance of host genetics. Genes Immun 4(1):4–11CrossRefPubMed
3.
Zurück zum Zitat Korbel DS, Schneider BE, Schaible UE (2008) Innate immunity in tuberculosis: myths and truth. Microbes Infect 10(9):995–1004CrossRefPubMed Korbel DS, Schneider BE, Schaible UE (2008) Innate immunity in tuberculosis: myths and truth. Microbes Infect 10(9):995–1004CrossRefPubMed
4.
Zurück zum Zitat van de Vosse E, Hoeve MA, Ottenhoff TH (2004) Human genetics of intracellular infectious diseases: molecular and cellular immunity against mycobacteria and salmonellae. Lancet Infect Dis 4(12):739–749CrossRefPubMed van de Vosse E, Hoeve MA, Ottenhoff TH (2004) Human genetics of intracellular infectious diseases: molecular and cellular immunity against mycobacteria and salmonellae. Lancet Infect Dis 4(12):739–749CrossRefPubMed
5.
Zurück zum Zitat Selvaraj P, Alagarasu K, Harishankar M, Vidyarani M, Nisha Rajeswari D, Narayanan PR (2008) Cytokine gene polymorphisms and cytokine levels in pulmonary tuberculosis. Cytokine 43(1):26–33CrossRefPubMed Selvaraj P, Alagarasu K, Harishankar M, Vidyarani M, Nisha Rajeswari D, Narayanan PR (2008) Cytokine gene polymorphisms and cytokine levels in pulmonary tuberculosis. Cytokine 43(1):26–33CrossRefPubMed
6.
Zurück zum Zitat Mendez-Samperio P (2010) Role of interleukin-12 family cytokines in the cellular response to mycobacterial disease. Int J Infect Dis 14(5):e366–e371CrossRefPubMed Mendez-Samperio P (2010) Role of interleukin-12 family cytokines in the cellular response to mycobacterial disease. Int J Infect Dis 14(5):e366–e371CrossRefPubMed
7.
Zurück zum Zitat Wakeham J, Wang J, Magram J, Croitoru K, Harkness R, Dunn P, Zganiacz A, Xing Z (1998) Lack of both types 1 and 2 cytokines, tissue inflammatory responses, and immune protection during pulmonary infection by Mycobacterium bovis bacille Calmette-Guerin in IL-12-deficient mice. J Immunol 160(12):6101–6111PubMed Wakeham J, Wang J, Magram J, Croitoru K, Harkness R, Dunn P, Zganiacz A, Xing Z (1998) Lack of both types 1 and 2 cytokines, tissue inflammatory responses, and immune protection during pulmonary infection by Mycobacterium bovis bacille Calmette-Guerin in IL-12-deficient mice. J Immunol 160(12):6101–6111PubMed
8.
Zurück zum Zitat Cooper AM, Magram J, Ferrante J, Orme IM (1997) Interleukin 12 (IL-12) is crucial to the development of protective immunity in mice intravenously infected with Mycobacterium tuberculosis. J Exp Med 186(1):39–45CrossRefPubMed Cooper AM, Magram J, Ferrante J, Orme IM (1997) Interleukin 12 (IL-12) is crucial to the development of protective immunity in mice intravenously infected with Mycobacterium tuberculosis. J Exp Med 186(1):39–45CrossRefPubMed
9.
Zurück zum Zitat Cooper AM, Khader SA (2008) The role of cytokines in the initiation, expansion, and control of cellular immunity to tuberculosis. Immunol Rev 226:191–204CrossRefPubMed Cooper AM, Khader SA (2008) The role of cytokines in the initiation, expansion, and control of cellular immunity to tuberculosis. Immunol Rev 226:191–204CrossRefPubMed
10.
Zurück zum Zitat Condos R, Rom WN, Liu YM, Schluger NW (1998) Local immune responses correlate with presentation and outcome in tuberculosis. Am J Respir Crit Care Med 157(3 Pt 1):729–735PubMed Condos R, Rom WN, Liu YM, Schluger NW (1998) Local immune responses correlate with presentation and outcome in tuberculosis. Am J Respir Crit Care Med 157(3 Pt 1):729–735PubMed
11.
Zurück zum Zitat Peng JC, Abu Bakar S, Richardson MM, Jonsson JJ, Frazer IH, Nielsen LK, Morahan G, Thomas R (2006) IL10 and IL12B polymorphisms each influence IL-12p70 secretion by dendritic cells in response to LPS. Immunol Cell Biol 84(2):227–232CrossRefPubMed Peng JC, Abu Bakar S, Richardson MM, Jonsson JJ, Frazer IH, Nielsen LK, Morahan G, Thomas R (2006) IL10 and IL12B polymorphisms each influence IL-12p70 secretion by dendritic cells in response to LPS. Immunol Cell Biol 84(2):227–232CrossRefPubMed
12.
Zurück zum Zitat Wang J, Shen H (2009) Review of cigarette smoking and tuberculosis in China: intervention is needed for smoking cessation among tuberculosis patients. BMC Public Health 9:292CrossRefPubMed Wang J, Shen H (2009) Review of cigarette smoking and tuberculosis in China: intervention is needed for smoking cessation among tuberculosis patients. BMC Public Health 9:292CrossRefPubMed
13.
Zurück zum Zitat Pravica V, Perrey C, Stevens A, Lee JH, Hutchinson IV (2000) A single nucleotide polymorphism in the first intron of the human IFN-gamma gene: absolute correlation with a polymorphic CA microsatellite marker of high IFN-gamma production. Hum Immunol 61(9):863–866CrossRefPubMed Pravica V, Perrey C, Stevens A, Lee JH, Hutchinson IV (2000) A single nucleotide polymorphism in the first intron of the human IFN-gamma gene: absolute correlation with a polymorphic CA microsatellite marker of high IFN-gamma production. Hum Immunol 61(9):863–866CrossRefPubMed
14.
Zurück zum Zitat Matsui M (2007) Roles of the novel interleukin-12-associated cytokine, interleukin-23, in the regulation of T-cell-mediated immunity. Hepatol Res 37(Suppl 3):S310–S318CrossRefPubMed Matsui M (2007) Roles of the novel interleukin-12-associated cytokine, interleukin-23, in the regulation of T-cell-mediated immunity. Hepatol Res 37(Suppl 3):S310–S318CrossRefPubMed
15.
Zurück zum Zitat Filipe-Santos O, Bustamante J, Chapgier A, Vogt G, de Beaucoudrey L, Feinberg J, Jouanguy E, Boisson-Dupuis S, Fieschi C, Picard C, Casanova JL (2006) Inborn errors of IL-12/23-and IFN-gamma-mediated immunity: molecular, cellular, and clinical features. Semin Immunol 18(6):347–361CrossRefPubMed Filipe-Santos O, Bustamante J, Chapgier A, Vogt G, de Beaucoudrey L, Feinberg J, Jouanguy E, Boisson-Dupuis S, Fieschi C, Picard C, Casanova JL (2006) Inborn errors of IL-12/23-and IFN-gamma-mediated immunity: molecular, cellular, and clinical features. Semin Immunol 18(6):347–361CrossRefPubMed
16.
Zurück zum Zitat Yilmaz V, Yentur SP, Saruhan-Direskeneli G (2005) IL-12 and IL-10 polymorphisms and their effects on cytokine production. Cytokine 30(4):188–194CrossRefPubMed Yilmaz V, Yentur SP, Saruhan-Direskeneli G (2005) IL-12 and IL-10 polymorphisms and their effects on cytokine production. Cytokine 30(4):188–194CrossRefPubMed
17.
Zurück zum Zitat Ma X, Reich RA, Gonzalez O, Pan X, Fothergill AK, Starke JR, Teeter LD, Musser JM, Graviss EA (2003) No evidence for association between the polymorphism in the 3′ untranslated region of interleukin-12B and human susceptibility to tuberculosis. J Infect Dis 188(8):1116–1118CrossRefPubMed Ma X, Reich RA, Gonzalez O, Pan X, Fothergill AK, Starke JR, Teeter LD, Musser JM, Graviss EA (2003) No evidence for association between the polymorphism in the 3′ untranslated region of interleukin-12B and human susceptibility to tuberculosis. J Infect Dis 188(8):1116–1118CrossRefPubMed
18.
Zurück zum Zitat Pacheco AG, Cardoso CC, Moraes MO (2008) IFNG +874 T/A, IL10-1082G/A and TNF-308G/A polymorphisms in association with tuberculosis susceptibility: a meta-analysis study. Hum Genet 123(5):477–484CrossRefPubMed Pacheco AG, Cardoso CC, Moraes MO (2008) IFNG +874 T/A, IL10-1082G/A and TNF-308G/A polymorphisms in association with tuberculosis susceptibility: a meta-analysis study. Hum Genet 123(5):477–484CrossRefPubMed
19.
Zurück zum Zitat Rossouw M, Nel HJ, Cooke GS, van Helden PD, Hoal EG (2003) Association between tuberculosis and a polymorphic NFkappaB binding site in the interferon gamma gene. Lancet 361(9372):1871–1872CrossRefPubMed Rossouw M, Nel HJ, Cooke GS, van Helden PD, Hoal EG (2003) Association between tuberculosis and a polymorphic NFkappaB binding site in the interferon gamma gene. Lancet 361(9372):1871–1872CrossRefPubMed
20.
Zurück zum Zitat Wu F, Qu Y, Tang Y, Cao D, Sun P, Xia Z (2008) Lack of association between cytokine gene polymorphisms and silicosis and pulmonary tuberculosis in Chinese iron miners. J Occup Health 50(6):445–454CrossRefPubMed Wu F, Qu Y, Tang Y, Cao D, Sun P, Xia Z (2008) Lack of association between cytokine gene polymorphisms and silicosis and pulmonary tuberculosis in Chinese iron miners. J Occup Health 50(6):445–454CrossRefPubMed
21.
Zurück zum Zitat Ding S, Li L, Zhu X (2008) Polymorphism of the interferon-gamma gene and risk of tuberculosis in a southeastern Chinese population. Hum Immunol 69(2):129–133CrossRefPubMed Ding S, Li L, Zhu X (2008) Polymorphism of the interferon-gamma gene and risk of tuberculosis in a southeastern Chinese population. Hum Immunol 69(2):129–133CrossRefPubMed
22.
Zurück zum Zitat Tso HW, Ip WK, Chong WP, Tam CM, Chiang AK, Lau YL (2005) Association of interferon gamma and interleukin 10 genes with tuberculosis in Hong Kong Chinese. Genes Immun 6(4):358–363CrossRefPubMed Tso HW, Ip WK, Chong WP, Tam CM, Chiang AK, Lau YL (2005) Association of interferon gamma and interleukin 10 genes with tuberculosis in Hong Kong Chinese. Genes Immun 6(4):358–363CrossRefPubMed
23.
Zurück zum Zitat Ansari A, Talat N, Jamil B, Hasan Z, Razzaki T, Dawood G, Hussain R (2009) Cytokine gene polymorphisms across tuberculosis clinical spectrum in Pakistani patients. PLoS ONE 4(3):e4778CrossRefPubMed Ansari A, Talat N, Jamil B, Hasan Z, Razzaki T, Dawood G, Hussain R (2009) Cytokine gene polymorphisms across tuberculosis clinical spectrum in Pakistani patients. PLoS ONE 4(3):e4778CrossRefPubMed
24.
Zurück zum Zitat Shibasaki M, Yagi T, Yatsuya H, Okamoto M, Nishikawa M, Baba H, Hashimoto N, Senda K, Kawabe T, Nakashima K, Imaizumi K, Shimokata K, Hasegawa Y (2009) An influence of interferon-gamma gene polymorphisms on treatment response to tuberculosis in Japanese population. J Infect 58(6):467–469CrossRefPubMed Shibasaki M, Yagi T, Yatsuya H, Okamoto M, Nishikawa M, Baba H, Hashimoto N, Senda K, Kawabe T, Nakashima K, Imaizumi K, Shimokata K, Hasegawa Y (2009) An influence of interferon-gamma gene polymorphisms on treatment response to tuberculosis in Japanese population. J Infect 58(6):467–469CrossRefPubMed
25.
Zurück zum Zitat Jang SY, Kim MK, Lee KR, Park MS, Kim BC, Cho KH, Lee MC, Kim YS (2009) Gene-to-gene interaction between sodium channel-related genes in determining the risk of antiepileptic drug resistance. J Korean Med Sci 24(1):62–68CrossRefPubMed Jang SY, Kim MK, Lee KR, Park MS, Kim BC, Cho KH, Lee MC, Kim YS (2009) Gene-to-gene interaction between sodium channel-related genes in determining the risk of antiepileptic drug resistance. J Korean Med Sci 24(1):62–68CrossRefPubMed
Metadaten
Titel
Association of genetic polymorphisms in the IL12-IFNG pathway with susceptibility to and prognosis of pulmonary tuberculosis in a Chinese population
verfasst von
J. Wang
S. Tang
H. Shen
Publikationsdatum
01.10.2010
Verlag
Springer-Verlag
Erschienen in
European Journal of Clinical Microbiology & Infectious Diseases / Ausgabe 10/2010
Print ISSN: 0934-9723
Elektronische ISSN: 1435-4373
DOI
https://doi.org/10.1007/s10096-010-0985-0

Weitere Artikel der Ausgabe 10/2010

European Journal of Clinical Microbiology & Infectious Diseases 10/2010 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.