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Association between tumor necrosis factor-a promoter -308 A/G polymorphism and susceptibility to sepsis and sepsis mortality: A systematic review and meta-analysis

Teuffel, Oliver MD; Ethier, Marie-Chantal BSc; Beyene, Joseph PhD; Sung, Lillian MD, PhD

doi: 10.1097/CCM.0b013e3181b42af0
Review Article

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).

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The authors have no potential conflicts of interest to disclose.

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© 2010 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins