Haplotypes composed of minor frequency single nucleotide polymorphisms of the TNF gene protect from progression into sepsis: A study using the new sepsis classification. (February 2018)

• Record Type: Journal Article
• Authors: Retsas, Theodoros; Huse, Klaus; Lazaridis, Lazaros-Dimitrios; Karampela, Niki; Bauer, Michael; Platzer, Matthias; Kolonia, Virginia; Papageorgiou, Eirini; Giamarellos-Bourboulis, Evangelos J.; Dimopoulos, George
• Is Part Of: International journal of infectious diseases. Volume 67(2018)
• Page Start: 102
• Page End: 106
• Publication Date: 2018-02
• Subjects: Tumour necrosis factor alpha -- Single nucleotide polymorphism -- Sepsis -- Haplotype; Communicable diseases -- Periodicals; Communicable Diseases -- Periodicals; Communicable diseases; Periodicals; Electronic journals; 616.9
• DOI: 10.1016/j.ijid.2017.12.008
• Languages: English
• ISSNs: 1201-9712

Abstract

Highlights: Carriage of minor frequency single nucleotide polymorphism (SNP) haplotypes was found to protect against the development of sepsis. Carriage of minor frequency SNP haplotypes did not affect patient 28-day outcomes. Serum levels of tumour necrosis factor alpha (TNF-α) were higher in patients with sepsis who carried two h1 alleles. 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.