Format

Send to

Choose Destination
Int J Infect Dis. 2018 Feb;67:102-106. doi: 10.1016/j.ijid.2017.12.008. Epub 2017 Dec 21.

Haplotypes composed of minor frequency single nucleotide polymorphisms of the TNF gene protect from progression into sepsis: A study using the new sepsis classification.

Author information

1
Department of Therapeutics, National and Kapodistrian University of Athens, Athens, Greece.
2
Genome Analysis, Leibniz Institute on Aging - Fritz Lipmann Institute, Jena, Germany.
3
Fourth Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece.
4
Intensive Care Unit, Korgialeneio Benakeio General Hospital, Athens, Greece.
5
Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany; Department of Anaesthesiology and Intensive Care Unit, Jena University Hospital, Jena, Germany.
6
Second Department of Internal Medicine, Sismanogleion General Hospital, Athens, Greece.
7
Intensive Care Unit, Thessaloniki Theageneio General Hospital, Thessaloniki, Greece.
8
Fourth Department of Internal Medicine, National and Kapodistrian University of Athens, Athens, Greece; Center for Sepsis Control and Care, Jena University Hospital, Jena, Germany. Electronic address: egiamarel@med.uoa.gr.
9
Second Department of Critical Care Medicine, National and Kapodistrian University of Athens, Athens, Greece.

Abstract

OBJECTIVES:

Several articles have provided conflicting results regarding the role of single nucleotide polymorphisms (SNPs) in the promoter region of the TNF gene in susceptibility to sepsis. Former articles have been based on previous definitions of sepsis. This study investigated the influence of TNF haplotypes on the development of sepsis using the new Sepsis-3 definitions.

METHODS:

DNA was isolated from patients suffering from infection and systemic inflammatory response syndrome. Haplotyping was performed for six SNPs of TNF. The serum levels of tumour necrosis factor alpha (TNF-α) of these patients were measured using an enzyme immunosorbent assay. Patients were classified into infection and sepsis categories using the Sepsis-3 definitions. Associations between the TNF haplotypes and the clinical characteristics and serum TNF-α levels of the patients were examined.

RESULTS:

The most common TNF haplotype h1 was composed of major alleles of the studied SNPs. Carriage of haplotypes composed of minor frequency alleles was associated with a lower risk of developing sepsis (odds ratio 0.41, 95% confidence interval 0.19-0.88, p=0.022), but this did not affect the 28-day outcome. Serum TNF-α levels were significantly higher among patients homozygous for h1 haplotypes who developed sepsis compared to infection (p=0.032); a similar result was not observed for patients carrying other haplotypes.

CONCLUSIONS:

Haplotypes containing minor frequency SNP alleles of TNF protect against the development of sepsis without affecting the outcome.

KEYWORDS:

Haplotype; Sepsis; Single nucleotide polymorphism; Tumour necrosis factor alpha

PMID:
29274398
DOI:
10.1016/j.ijid.2017.12.008
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center