Association between the -308G/A Polymorphism of TNF-<i>α</i> and Susceptibility of Inflammatory Bowel Disease: A Meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

 LIUZhou ,  DONGWei-guo , WANGJun , ZHANGJi-xiang , GUOXu-feng

Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan 430060, China;

Corresponding author：

DONGWei-guo, Email: dwg@whu.edu.cn

Keywords：

Tumor necrosis factor-α; Polymorphism; Inflammatory bowel disease; Case-control study; Systematic review; Meta-analysis

DOI：

10.7507/1672-2531.20150071

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Objective To systematically review the tumor necrosis factor-α (TNF-α) -308G/A polymorphism and the risk of inflammatory bowel disease (IBD). Methods All eligible case-control studies published up to Jan 25th 2015 were identified by searching PubMed, EMbase, CNKI, WanFang Data, CBM and VIP databases. Two reviewers independently screened the studies according to the inclusion and exclusion criteria, extracted data and assessed methodological quality of included studies. Then, meta-analysis was performed using RevMan 5.2 and Stata 12.0 softwares. Results A total of 20 studies involving 2 860 IBD cases and 5 033 controls were included. The results of meta-analysis showed:Compared with the wild genotype GG, genotype GA, AA and genotype GA+AA were associated with susceptibility of ulcerative colitis (UC) (GA vs. GG:OR=1.45, 95%CI 1.02 to 2.07, P=0.04; AA vs. GG:OR=2.01, 95%CI 1.32 to 3.05, P=0.001; GA+AA vs. GG:OR=1.51, 95%CI 1.07 to 2.13, P=0.02); Compared with genotype GA+AA, genotype AA increased the risk of UC (AA vs. GA+GG:OR=1.92, 95%CI 1.26 to 2.91, P=0.002); allele A did not increase the risk of UC; Compared with genotype GG, genotype AA increased the risk of Crohn disease (CD) (AA vs. GG:OR=1.49, 95%CI 1.07 to 2.08, P=0.02); Compared with genotype GA+GG, while genotype AA increased the risk of CD (AA vs. GA+GG:OR=1.50, 95%CI 1.08 to 2.09, P=0.02); genotype GA, GA+AA and allele A did not increase the risk of CD. In stratification analyses by ethnicity, we found that the TNF-α-308G/A was significat associated with IBD in Europeans. Conclusion Current evidence indicates that TNF-α-308G/A polymorphism is associated with the susceptibility of IBD, genotype GA, AA and GA+AA increase the risk of suffering from UC while genotype AA increase the risk of suffering from CD. Due to the limited quantity of the included studies, more researches are needed to verify the above conclusion.

Citation： LIUZhou, DONGWei-guo, WANGJun, ZHANGJi-xiang, GUOXu-feng. Association between the -308G/A Polymorphism of TNF-α and Susceptibility of Inflammatory Bowel Disease: A Meta-analysis. Chinese Journal of Evidence-Based Medicine, 2015, 15(4): 419-424. doi: 10.7507/1672-2531.20150071 Copy

1.	Merger M, Croitoru K. Infections in the immunopathogenesis of chronic inflammatory bowel disease. Semin Immunol, 1988, 10(1):69-78.
2.	Papadakis KA, Targan SR. Current theories on the causes of inflammatory bowel disease. Gastroenterol Clin North Am, 1999, 28(2):283-296.
3.	周国胜, 吴正祥. 炎症性肠病与肿瘤坏死因子基因多态性的研究进展. 世界华人消化杂志, 2008, 16(21):2390-2394.
4.	Jang WH, Yang YI, Yea SS, et al. The -238 tumor necrosis factor alpha promoter polymorphism is associated with decreased susceptibility to cancers. Cancer Lett, 2001, 166(1):41-46.
5.	Wilson AG, di Giovine FS, Blakemore AI, et al. Single base polymorphism in the human tumour necrosis factor alpha (TNF alpha) gene detectable by Nco I restriction of PCR product. Hum Mol Genet, 1992, 1(5):353.
6.	Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol, 2010, 25(9):603-605.
7.	Bouma G, Xia B, Crusius JB, et al. Distribution of four polymorphisms in the tumour necrosis factor (TNF) genes in patients with inflammatory bowel disease (IBD). Clin Exp Immunol, 1996, 103(3):391-396.
8.	Sashio H, Tamura K, Ito R, et al. Polymorphisms of the TNF gene and the TNF receptor superfamily member 1B gene are associated with susceptibility to ulcerative colitis and crohn's disease respectively. Immunogenetics, 2002, 53(12):1020-1027.
9.	Martin K, Radlmayr M, Borchers R, et al. Candidate genes colocalized to linkage regions in inflammatory bowel disease. Digestion, 2002, 66(2):121-126.
10.	González S, Rodrigo L, Martinez-Borra J, et al. TNF-alpha-308A promoter polymorphism is associated with enhanced TNF-alpha production and inflammatory activity in Crohn's patients with fistulizing disease. Am J Gastroenterol, 2003, 98(5):1101-1106.
11.	Balding J, Livingstone WJ, Conroy J, et al. Inflammatory bowel disease:the role of inflammatory cytokine gene polymorphisms. Mediators Inflammm, 2004, 13(3):181-187.
12.	Fowler EV, Eri R, Hume G, et al. TNF alpha and IL10 SNPs act together to predict disease behavior in Crohn's disease. J Med Genet, 2005, 42(6):523-528.
13.	Cantor MJ, Nickerson P, Bernstein CN, et al. The role of cytokine gene polymorphisms in determining disease susceptibility and phenotype in inflammatory bowel disease. Am J Gastroenterol, 2005, 100(5):1134-1142.
14.	Song Y, Wu KC, Zhang L, et al. Correlation between a gene polymorphism of tumor necrosis factor and inflammatory bowel disease. Chin J Dig Dis, 2005, 6(4):170-174.
15.	Zipperlen K, Peddle L, Melay B, et al. Association of TNF-alpha polymorphisms in Crohn disease. Hum Immunol, 2005, 66(1):56-59.
16.	Sýkora J, Subrt I, Didek P, et al. Cytokine tumor necrosis factor-alpha A promoter gene polymorphism at position -308 G>A and pediatric inflammatory bowel disease:implications in ulcerative colitis and Crohn's disease. J Pediatr Gastroenterol Nutr, 2006, 42(5):479-487.
17.	Cao Q, Gao M, Zhou G, et al. Association of tumor necrosis factor polymorphisms with susceptibility to ulcerative colitis in Chinese Han population. Chin J Dig, 2006, 26 (7):460-463.
18.	Celik Y, Dagli U, Kilic MY, et al. Cytokine gene polymorphisms in Turkish patients with inflammatory bowel disease. Scand J Gastroenterol, 2006, 41(5):559-565.
19.	Ferguson LR, Huebner C, Petermann I, et al. Single nucleotide polymorphism in the tumor necrosis factor-alpha gene affects inflammatory bowel disease risk. World J Gastroenterol, 2008, 14 (29):4652-4661.
20.	Bonyadi M, Abdolmohammadi R, Jahanafrooz Z, et al. TNF-alpha gene polymorphisms in Iranian Azari Turkish patients with inflammatory bowel disease. Saudi J Gastroenterol, 2014, 20(2):108-112.
21.	Yang SK, Lee SG, Cho YK, et al. Association of TNF-alpha/LTA polymorphisms with Crohn's disease in Koreans. Cytokine, 2006, 35(1-2):13-20.
22.	Cucchiara S, Latiano A, Palmieri O, et al. Polymorphisms of tumor necrosis factor-alpha but not MDR1 influence response to medical therapy in pediatric-onset inflammatory bowel disease. J Pediatr Gastroenterol Nutr, 2007, 44(2):171-179.
23.	Castro-Santos P, Suarez A, Lopez-Rivas L, et al. TNF alpha and IL-10 gene polymorphisms in inflammatory bowel disease. Association of -1082 AA low producer IL-10 genotype with steroid dependency. Am J Gastroenterol, 2006, 101(5):1039-1047.
24.	Yamamoto-Furusho JK, Uscanga LF, Vargas-Alarcon G, et al. Polymorphisms in the promoter region of tumor necrosis factor-αand the HLA-DRB1 locus in Mexican Mestizo patients with ulcerative colitis. Immunol Lett, 2004, 95(1):31-35.
25.	Hradsky O, Lenicek M, Dusatkova P, et al. Variants of CARD15, TNFA and PTPN22 and susceptibility to Crohn's disease in the Czech population:high frequency of the CARD151007fs. Tissue Antigens, 2008, 71(6):538-547.
26.	Ferreira AC, Almeida S, Tavares M, et al. NOD2/CARD15 and TNFA, but not IL1B and IL1RN, are associated with Crohn's disease. Inflamm Bowel Dis, 2005, 11(4):331-339.
27.	Skoog T, van't Hooft FM, Kallin B, et al. A common functional polymorphism (C->A substitution at position -863) in the promoter region of the tumour necrosis factor-alpha (TNF-alpha) gene associated with reduced circulation levels of TNF-alpha. Hum Mol Genet, 1999, 8(8):1441-1447.
28.	Hoffmann SC, Stanley EM, Cox ED, et al. Ethnicity greatly influences cytokine gene polymorphism distribution. Am J Transplant, 2002, 2(6):560-567.
29.	余灿清, 詹思延. 如何撰写高质量的流行病学研究论文第二讲遗传关联性研究及其Meta分析的报告规范. 中华流行病学杂志, 2006, 27 (8):728-730.
30.	Indaram AV, Visvalingam V, Locke M, et al. Mucosal cytokine production in radiation-induced proctosigmoiditis compared with inflammatory bowel disease. Am J Gastroenterol, 2000, 95(5):1221-1225.
31.	严瑾, 欧阳钦, 刘卫平, 等. 肿瘤坏死因子-α在溃疡性结肠炎中的表达及其作用探讨. 胃肠病学, 2005, 10(5):269-272.
32.	Vemeire S, Rutgeerts P. Current status of genetics research in inflammatory bowel disease. Genes Immun, 2005, 6(8):637-645.
33.	Barnich N, Carvalho FA, Glasser AL, et al. CEACAM6 acts as a receptor for adherent-invasive E. coli, supporting ileal mucosa colonization in Crohn disease. J Chin Invest, 2007, 117(6):1566-1574.
34.	Berndt U, Bartsch S, Philipsen L, et al. Proteomic analysis of the inflamed intestinal mucosa reveals distinctive immune response profiles in Crohn's disease and ulcerative colitis. J Immunol, 2007, 179(1):295-304.

1. Merger M, Croitoru K. Infections in the immunopathogenesis of chronic inflammatory bowel disease. Semin Immunol, 1988, 10(1):69-78.
2. Papadakis KA, Targan SR. Current theories on the causes of inflammatory bowel disease. Gastroenterol Clin North Am, 1999, 28(2):283-296.
3. 周国胜, 吴正祥. 炎症性肠病与肿瘤坏死因子基因多态性的研究进展. 世界华人消化杂志, 2008, 16(21):2390-2394.
4. Jang WH, Yang YI, Yea SS, et al. The -238 tumor necrosis factor alpha promoter polymorphism is associated with decreased susceptibility to cancers. Cancer Lett, 2001, 166(1):41-46.
5. Wilson AG, di Giovine FS, Blakemore AI, et al. Single base polymorphism in the human tumour necrosis factor alpha (TNF alpha) gene detectable by Nco I restriction of PCR product. Hum Mol Genet, 1992, 1(5):353.
6. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol, 2010, 25(9):603-605.
7. Bouma G, Xia B, Crusius JB, et al. Distribution of four polymorphisms in the tumour necrosis factor (TNF) genes in patients with inflammatory bowel disease (IBD). Clin Exp Immunol, 1996, 103(3):391-396.
8. Sashio H, Tamura K, Ito R, et al. Polymorphisms of the TNF gene and the TNF receptor superfamily member 1B gene are associated with susceptibility to ulcerative colitis and crohn's disease respectively. Immunogenetics, 2002, 53(12):1020-1027.
9. Martin K, Radlmayr M, Borchers R, et al. Candidate genes colocalized to linkage regions in inflammatory bowel disease. Digestion, 2002, 66(2):121-126.
10. González S, Rodrigo L, Martinez-Borra J, et al. TNF-alpha-308A promoter polymorphism is associated with enhanced TNF-alpha production and inflammatory activity in Crohn's patients with fistulizing disease. Am J Gastroenterol, 2003, 98(5):1101-1106.
11. Balding J, Livingstone WJ, Conroy J, et al. Inflammatory bowel disease:the role of inflammatory cytokine gene polymorphisms. Mediators Inflammm, 2004, 13(3):181-187.
12. Fowler EV, Eri R, Hume G, et al. TNF alpha and IL10 SNPs act together to predict disease behavior in Crohn's disease. J Med Genet, 2005, 42(6):523-528.
13. Cantor MJ, Nickerson P, Bernstein CN, et al. The role of cytokine gene polymorphisms in determining disease susceptibility and phenotype in inflammatory bowel disease. Am J Gastroenterol, 2005, 100(5):1134-1142.
14. Song Y, Wu KC, Zhang L, et al. Correlation between a gene polymorphism of tumor necrosis factor and inflammatory bowel disease. Chin J Dig Dis, 2005, 6(4):170-174.
15. Zipperlen K, Peddle L, Melay B, et al. Association of TNF-alpha polymorphisms in Crohn disease. Hum Immunol, 2005, 66(1):56-59.
16. Sýkora J, Subrt I, Didek P, et al. Cytokine tumor necrosis factor-alpha A promoter gene polymorphism at position -308 G>A and pediatric inflammatory bowel disease:implications in ulcerative colitis and Crohn's disease. J Pediatr Gastroenterol Nutr, 2006, 42(5):479-487.
17. Cao Q, Gao M, Zhou G, et al. Association of tumor necrosis factor polymorphisms with susceptibility to ulcerative colitis in Chinese Han population. Chin J Dig, 2006, 26 (7):460-463.
18. Celik Y, Dagli U, Kilic MY, et al. Cytokine gene polymorphisms in Turkish patients with inflammatory bowel disease. Scand J Gastroenterol, 2006, 41(5):559-565.
19. Ferguson LR, Huebner C, Petermann I, et al. Single nucleotide polymorphism in the tumor necrosis factor-alpha gene affects inflammatory bowel disease risk. World J Gastroenterol, 2008, 14 (29):4652-4661.
20. Bonyadi M, Abdolmohammadi R, Jahanafrooz Z, et al. TNF-alpha gene polymorphisms in Iranian Azari Turkish patients with inflammatory bowel disease. Saudi J Gastroenterol, 2014, 20(2):108-112.
21. Yang SK, Lee SG, Cho YK, et al. Association of TNF-alpha/LTA polymorphisms with Crohn's disease in Koreans. Cytokine, 2006, 35(1-2):13-20.
22. Cucchiara S, Latiano A, Palmieri O, et al. Polymorphisms of tumor necrosis factor-alpha but not MDR1 influence response to medical therapy in pediatric-onset inflammatory bowel disease. J Pediatr Gastroenterol Nutr, 2007, 44(2):171-179.
23. Castro-Santos P, Suarez A, Lopez-Rivas L, et al. TNF alpha and IL-10 gene polymorphisms in inflammatory bowel disease. Association of -1082 AA low producer IL-10 genotype with steroid dependency. Am J Gastroenterol, 2006, 101(5):1039-1047.
24. Yamamoto-Furusho JK, Uscanga LF, Vargas-Alarcon G, et al. Polymorphisms in the promoter region of tumor necrosis factor-αand the HLA-DRB1 locus in Mexican Mestizo patients with ulcerative colitis. Immunol Lett, 2004, 95(1):31-35.
25. Hradsky O, Lenicek M, Dusatkova P, et al. Variants of CARD15, TNFA and PTPN22 and susceptibility to Crohn's disease in the Czech population:high frequency of the CARD151007fs. Tissue Antigens, 2008, 71(6):538-547.
26. Ferreira AC, Almeida S, Tavares M, et al. NOD2/CARD15 and TNFA, but not IL1B and IL1RN, are associated with Crohn's disease. Inflamm Bowel Dis, 2005, 11(4):331-339.
27. Skoog T, van't Hooft FM, Kallin B, et al. A common functional polymorphism (C->A substitution at position -863) in the promoter region of the tumour necrosis factor-alpha (TNF-alpha) gene associated with reduced circulation levels of TNF-alpha. Hum Mol Genet, 1999, 8(8):1441-1447.
28. Hoffmann SC, Stanley EM, Cox ED, et al. Ethnicity greatly influences cytokine gene polymorphism distribution. Am J Transplant, 2002, 2(6):560-567.
29. 余灿清, 詹思延. 如何撰写高质量的流行病学研究论文第二讲遗传关联性研究及其Meta分析的报告规范. 中华流行病学杂志, 2006, 27 (8):728-730.
30. Indaram AV, Visvalingam V, Locke M, et al. Mucosal cytokine production in radiation-induced proctosigmoiditis compared with inflammatory bowel disease. Am J Gastroenterol, 2000, 95(5):1221-1225.
31. 严瑾, 欧阳钦, 刘卫平, 等. 肿瘤坏死因子-α在溃疡性结肠炎中的表达及其作用探讨. 胃肠病学, 2005, 10(5):269-272.
32. Vemeire S, Rutgeerts P. Current status of genetics research in inflammatory bowel disease. Genes Immun, 2005, 6(8):637-645.
33. Barnich N, Carvalho FA, Glasser AL, et al. CEACAM6 acts as a receptor for adherent-invasive E. coli, supporting ileal mucosa colonization in Crohn disease. J Chin Invest, 2007, 117(6):1566-1574.
34. Berndt U, Bartsch S, Philipsen L, et al. Proteomic analysis of the inflamed intestinal mucosa reveals distinctive immune response profiles in Crohn's disease and ulcerative colitis. J Immunol, 2007, 179(1):295-304.

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Association between the -308G/A Polymorphism of TNF-α and Susceptibility of Inflammatory Bowel Disease: A Meta-analysis

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