@article{3107722,
    title = "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 = "Retsas, T. and Huse, K. and Lazaridis, L.-D. and Karampela, N. and Bauer, M. and Platzer, M. and Kolonia, V. and Papageorgiou, E. and Giamarellos-Bourboulis, E.J. and Dimopoulos, G.",
    journal = "International Journal of Infectious Diseases",
    year = "2018",
    volume = "67",
    pages = "102-106",
    publisher = "Elsevier B.V.",
    issn = "1201-9712",
    doi = "10.1016/j.ijid.2017.12.008",
    keywords = "tumor necrosis factor;  tumor necrosis factor, adult;  aged;  allele;  Article;  confidence interval;  controlled study;  disease classification;  disease course;  DNA isolation;  enzyme linked immunosorbent assay;  female;  gene frequency;  haplotype;  homozygosity;  human;  infection risk;  major clinical study;  male;  outcome assessment;  protein blood level;  sepsis;  sepsis 3 definition;  single nucleotide polymorphism;  step wise multiple regression;  systemic inflammatory response syndrome;  blood;  disease exacerbation;  gene frequency;  genetics;  haplotype;  middle aged;  sepsis;  very elderly;  young adult, Adult;  Aged;  Aged, 80 and over;  Alleles;  Disease Progression;  Female;  Gene Frequency;  Haplotypes;  Humans;  Male;  Middle Aged;  Polymorphism, Single Nucleotide;  Sepsis;  Tumor Necrosis Factor-alpha;  Young Adult",
    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. © 2017 The Author(s)"
}