Journal Information
Vol. 15. Issue 3.
Pages 231-238 (May - June 2011)
Share
Share
Download PDF
More article options
Vol. 15. Issue 3.
Pages 231-238 (May - June 2011)
Open Access
TNF -308G > A promoter polymorphism (rs1800629) and outcome from critical illness
Visits
3068
Diego D’Ávila Paskulin1, Paulo R.V. Fallavena2, Francis J.O. Paludo2, Thiago J. Borges3, Juliane B. Picanço2, Fernando S. Dias4, Clarice Sampaio Alho4,
Corresponding author
csalho@pucrs.br

Av. Ipiranga, 6681 P12 - 2° andar, Porto Alegre, RS, Brazil, 90619-900, Phone (fax): 55 51 33203545.
1 PhD Student, Universidade Federal do Rio Grande do Sul (UFRGS), Brazil
2 PhD Student, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Brazil
3 Biologist, MSc Student, PUCRS, Brazil
4 Researcher, PUCRS, Brazil
This item has received

Under a Creative Commons license
Article information
Abstract
Background

The susceptibility to adverse outcome from critical illness (occurrence of sepsis, septic shock, organ dysfunction/failure, and mortality) varies dramatically due to different degrees of inflammatory response. An over expression of tumor necrosis factor alpha (TNF-α) can lead to the progression of the inflammatory condition.

Objective

We assessed the relationship of the genotype distribution of -308G >A TNF-α polymorphism with regard to the development of sepsis, septic shock, higher organ dysfunction or mortality in critically ill patients.

Methods

Observational, hospital- based cohort study of 520 critically ill Caucasian patients from southern Brazil admitted to the general ICU of São Lucas Hospital, Porto Alegre, Brazil. Patients were monitored daily from the ICU admission day to hospital discharge or death, measuring SOFA score, sepsis, and septic shock occurrences. The −308G >A TNF-α SNP effect was analyzed in the entire patient group, in patients with sepsis (349/520), and in those who developed septic shock (248/520).

Results

The genotypic and allelic frequencies were −308GG=0.72; −308GA=0.27; −308AA=0.01; −308G=0.85; −308A=0.15. No associations were found with sepsis, septic shock, organ dysfunction, and/or mortality rates among the TNF-α genotypes. Our results reveal that the -308G >A TNF-α SNP alone was not predictive of severe outcomes in critically ill patients.

Conclusion

The principal novel input of this study was the larger sample size in an investigation with −308G > A TNF-α SNP. The presence of −308A allele is not associated with sepsis, septic shock, higher organ dysfunction or mortality in critically ill patients.

Keywords:
polymorphism
single nucleotide
tumor necrosis factor receptor
associated peptides and proteins
critical care
Full text is only aviable in PDF
References
[1.]
M. Resche-Rigon, E. Azoulay, S. Chevret.
Evaluating mortality in intensive care units: contribution of competing risks analyses.
Crit Care, 10 (2006), pp. 103
[2.]
K. Poikonen, T. Lajunen, S. Silvennoinen-Kassinen, et al.
Effects of CD14, TLR2, TLR4 LPB, and IL-6 Gene Polymorphisms on Chlamydia pneumoniae Growth in Human Macrophages In Vitro.
Scand J Immunol., 7 (2009), pp. 30-39
[3.]
R. Medzhitov, C.A. Janeway Jr..
Innate immunity: the virtues of a nonclonal system of recognition.
Cell, 91 (1997), pp. 295-298
[4.]
S.A. Arancibia, C.J. Beltran, I.M. Aguirre, P. Silva, et al.
Toll-like receptors are key participants in innate immune responses.
Biol Res, 40 (2007), pp. 97-112
[5.]
M.A. Dobrovolskaia, S.N. Vogel.
Toll receptors CD14, and macrophage activation and deactivation by LPS.
Microbes Infect, 4 (2002), pp. 903-914
[6.]
J.J. O'Shea, A. Ma, P. Lipsky.
Cytokines and Autoimmunity.
Nat Rev Immunol., 2 (2002), pp. 37-45
[7.]
R.M. Locksley, N. Killeen, M.J. Lenardo.
The TNF and TNF receptor superfamilies: integrating mammalian biology.
Cell, 104 (2001), pp. 487-501
[8.]
A.J. Schottelius, L.L. Moldawer, C.A. Dinarello, et al.
Biology of tumor necrosis factor-alpha - implications for psoriasis.
Exp Dermatol., 13 (2004), pp. 193-222
[9.]
L.J. Wood, L.M. Nail, A. Gilster, K.A. Winters.
Cancer chemotherapy- related symptoms: Evidence to suggest a role for proinflammatory cytokines.
Oncol Nurs Forum, 33 (2006), pp. 535-542
[10.]
A.G. Wilson, F.S. di Giovine, A.I. Blakemore, G.W. Duff.
Single base polymorphism in the human tumour necrosis factor alpha (TNF alpha) gene detectable by NcoI restriction of PCR product.
Hum Mol Genet., 1 (1992), pp. 353
[11.]
R.G. Wunderink, G.W. Waterer.
Genetics of sepsis and pneumonia.
Curr Opin Crit Care, 9 (2003), pp. 384-389
[12.]
S.S. Grohe, F. Stuber, M. Book.
TNF-a Promoter Polymorphism in Relation to TNF-a Production and Clinical Status in Cystic Fibrosis.
[13.]
K.M. Kroeger, K.S. Carville, L.J. Abraham.
The -308 tumor necrosis factor-α promoter polymorphism effects transcription.
Mol Immunol., 34 (1997), pp. 391-399
[14.]
A.G. Wilson, J.A. Symons, T.L. McDowell, et al.
Effects of a polymorphism in the human tumor necrosis factor-α promoter on transcriptional activation.
Immunol., 94 (1997), pp. 3195-3199
[15.]
B. Beutler.
Shock and tissue injury induced by recombinant human cachectin.
Science, 234 (1986), pp. 470-474
[16.]
F. Stüber, M. Petersen, F. Bokelmann, U. Schade.
A genomic polymorphism within the tumor necrosis factor locus influences plasma tumor necrosis factor-a concentrations and outcome of patients with severe sepsis.
Crit Care Med., 24 (1996), pp. 381-384
[17.]
J.P. Mira, A. Cariou, F. Grall, et al.
Association of TNF2, a TNFalpha promoter polymorphism, with septic shock susceptibility and mortality: a multicenter study.
JAMA, 282 (1999), pp. 561-568
[18.]
G.J. Tang, S.L. Huang, H.W. Yien, et al.
Tumor necrosis factor gene polymorphism and septic shock in surgical infection.
Crit Care Med., 28 (2000), pp. 2733-2736
[19.]
O. Appoloni, E. Dupont, M. Vandercruys, et al.
Association of Tumor Necrosis Factor-2 Allele with Plasma Tumor Necrosis Factor-alpha Levels and Mortality from Septic Shock.
Am J Med., 110 (2001), pp. 486-488
[20.]
G.W. Waterer, M.W. Quasney, R.M. Cantor, R.G. Wunderink.
Septic shock and respiratory failure in community-acquired pneumonia have different TNF polymorphism associations.
Am J Resp Crit Care Med., 163 (2001), pp. 1599-1604
[21.]
G.E. O’Keefe, D.L. Hybki, R.S. Munford.
The G-A single nucleotide polymorphism at the -308 position in the tumor necrosis factor-alpha promoter increases the risk for severe sepsis after trauma.
J Trauma, 52 (2002), pp. 817-825
[22.]
C.L. Reid, C. Perrey, V. Pravica, et al.
Genetic variation in proinflammatory and anti-inflammatory cytokine production in multiple organ dysfunction syndrome.
Crit Care Med., 30 (2002), pp. 2216-2221
[23.]
A.C. Gordon, A.L. Lagan, E. Aganna, et al.
TNF and TNFR polymorphisms in severe sepsis and septic shock: a prospective multicentre study.
Genes Immun., 5 (2004), pp. 631-640
[24.]
K.M. Jessen, S.B. Lindboe, A.L. Petersen, et al.
Common TNF-α, IL-1β, PAI-1, uPA, CD14 and TLR4 polymorphisms are not associated with disease severity or outcome from Gram negative sepsis.
BMC Infect Dis., 18 (2007), pp. 108
[25.]
American College of Chest Physicians/Society of Critical Care, Medicine, Consensus Conference.
definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis.
Crit Care Med., 20 (1992), pp. 864-874
[26.]
W.A. Knaus, E.A. Draper, D.P. Wagner, J.E. Zimmerman.
APACHE II: a severity of disease classification system.
Crit Care Med., 13 (1985), pp. 818-829
[27.]
J.L. Vincent, R. Moreno, J. Takala, et al.
The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine.
Int Care Med., 22 (1996), pp. 707-710
[28.]
D.K. Lahiri, J.I. Nurnberger Jr..
A rapid non-enzymatic method for the preparation of HMW DNA from blood for RFLP studies.
Nucl Acids Res., 19 (1991), pp. 5444
[29.]
I.A. Kauss, C.M. Grion, L.T. Cardoso, et al.
The epidemiology of sepsis in a Brazilian teaching hospital.
Braz J Infect Dis., 14 (2010), pp. 264-270
[30.]
J. Garnacho-Montero, T. Aldabo-Pallas, C. Garnacho-Montero, et al.
Timing of adequate antibiotic therapy is a greater determinant of outcome than are TNF and IL-10 polymorphisms in patients with sepsis.
Crit Care, 10 (2006), pp. R111
[31.]
M.F. Clark, S.V. Baudouin.
A systematic review of the quality of genetic association studies in human sepsis.
Int Care Med., 32 (2006), pp. 1706-1712
[32.]
C. Newton-Cheh, J.N. Hirschhorn.
Genetic association studies of complex traits design and analysis issues.
Mutation Research, 573 (2005), pp. 54-69
[33.]
K.E. Lohmueller, C.L. Pearce, M. Pike, et al.
Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease.
Nat Genet., 33 (2003), pp. 177-182
[34.]
L.R. Cardon, J.I. Bell.
Association study designs for complex diseases.
Nat Rev Genet., 2 (2001), pp. 91-99
[35.]
J.P.A. Ioannidis, T.A. Trikalinos, E.E. Ntzani, D.G. Contopoulos-Ioannidis.
Genetic associations in large versus small studies: an empirical assessment.
[36.]
J.A. Todd.
Statistical false positive or true disease pathway?.
Nat Genet., 38 (2006), pp. 731-733
[37.]
S.T. Bogardus Jr., J. Concato, A.R. Feinstein.
Clinical epidemiological quality in molecular genetic research: The need for methodological standards.
JAMA, 281 (1999), pp. 1919-1926
[38.]
NCI-NHGRI., Working Group on Replication in Association Studies.
Replicating genotype-phenotype associations.
Nature, 447 (2007), pp. 655-660
[39.]
E. Louis, D. Franchimont, A. Piron, et al.
Tumour necrosis factor (TNF) gene polymorphism influences TNF-alpha production in lipopolysaccharide (LPS)-stimulated whole blood cell culture in healthy humans.
Clin Exp Immunol., 113 (1998), pp. 401-406
[40.]
J. Cohen, J. Carlet.
INTERSEPT: An international, multicenter, placebo-controlled trial of monoclonal antibody to human tumor necrosis factor-alpha in patients with sepsis: International Sepsis Trial Study Group.
Crit Care Med., 24 (1996), pp. 1431-1440
[41.]
E. Abraham, A. Anzueto, G. Guttierez, et al.
Double-blind randomized controlled trial of monoclonal antibody to human tumour necrosis factor in the treatment of septic shock The NORASEPT II Study Group.
Lancet, 351 (1998), pp. 929-933
[42.]
H.M. Colhoun, P.M. McKeigue, G. Davey Smith.
Problems of reporting genetic associations with complex outcomes.
Lancet 2003, 8 (2003), pp. 865-872
[43.]
D.L. Peters, R.C. Barber, E.M. Flood, et al.
Methodologic quality and genotyping reproducibility in studies of tumor necrosis factor -308 G-A single nucleotide polymorphism and bacterial sepsis: implications for studies of complex traits.
Crit Care Med., 31 (2003), pp. 1691-1696
[44.]
S.H. Vitali, A.G. Randolph.
Assessing the quality of case-control association studies on the genetic basis of sepsis.
Pediatr Crit Care Med., 6 (2005), pp. S74-S77
[45.]
T.A. Trikalinos, G. Salanti, M.J. Khoury, J.P. Ioannidis.
Impact of violations and deviations in Hardy-Weinberg equilibrium on postulated gene-disease associations.
Am J Epidemiol., 15 (2006), pp. 300-309
[46.]
F.M. Salzano, N. Freire-Maia.
Problems in human biology. A study of Brazilian populations.
Wayne State University Press, (1970),
[47.]
F.C. Parra, R.C. Amado, J.R. Lambertucci, et al.
Color and genomic ancestry in Brazilians.
Proc Natl Acad Sci USA, 100 (2003), pp. 177-182
[48.]
Y. Watanabe, T. Muratake, N. Kaneko, N. Fukui, Y. Nara, T. Someya.
No ssociation between the tumor necrosis factor-alpha gene promoter polymorphisms and schizophrenia in a Japanese population.
Psychiatry Res., 153 (2007), pp. 1-6
[49.]
A.H. Hajeer.
Hutchinson IV. Influence of TNFalpha gene polymorphisms on TNFalpha production and disease.
Hum Immunol., 62 (2001), pp. 1191-1199
Copyright © 2011. Elsevier Editora Ltda.. All rights reserved
Download PDF
The Brazilian Journal of Infectious Diseases
Article options
Tools