Objective: The tumor necrosis factor (TNF)-α promoter −308 A/G polymorphism has been reported to be associated with sepsis with inconsistent results. We conducted a systematic review and meta-analysis to determine whether the TNF-α −308 A/G polymorphism TNF2 (G/A or A/A) confers susceptibility to sepsis or is associated with increased risk of death from sepsis.
Data Sources: We performed an electronic search of OVID MEDLINE from 1950 to June 2008 and EMBASE from 1980 to June 2008.
Study Selection: From 1935 reviewed study articles, 25 were included based on predefined inclusion criteria.
Data Extraction: Two reviewers independently extracted data onto standardized forms.
Data Synthesis: An association between development of sepsis and the TNF2 genotype was found in the overall population (odds ratio, 2.15; 95% confidence interval, 1.45–3.19; p < .01). Stratification by ethnicity indicated that the contribution to this observation may be stronger among the Asian population (odds ratio, 3.16; 95% confidence interval, 1.92 to 5.20; p < .01) compared with other ethnicities. There was no association between the TNF2 genotype and mortality from sepsis (odds ratio, 1.48; 95% confidence interval, 0.81 to 2.70; p = .20). However, when stratified for ethnicity, there may be an increased risk for fatal outcomes among Asians (odds ratio, 10.75; 95% confidence interval, 2.98 to 38.78; p < .01).
Conclusions: Our systematic review and meta-analysis demonstrates that the TNF2 polymorphism is associated with sepsis. However, TNF2 is not associated with sepsis mortality.
From the Division of Haematology/Oncology (OT, LS), Hospital for Sick Children, Toronto, Canada; Departments of Pediatrics (M-CE, JB, LS), Health Policy Management and Evaluation and Dalla Lana School of Public Health, University of Toronto, Toronto, Canada; and Biostatistics Methodology Unit (JB), Hospital for Sick Children, Toronto, Canada.
Dr. Sung is supported by a Career Development Award with the Child Health Clinician Scientist Training Program, a strategic training program of the Canadian Institutes of Health Research. Dr. Beyene would like to acknowledge funding from the Canadian Institute of Health Research, CIHR (Grant 84392).
Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML and PDF versions of this article on the journal's Web site (www.ccmjournal.org). Two supplemental figures can be viewed through these links (Supplemental Digital Content 1, http://links.lww.com/CCM/A70; and Supplemental Digital Content 2, http://links.lww.com/CCM/A71).
The authors have no potential conflicts of interest to disclose.
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