Haplotypes composed of minor frequency single nucleotide polymorphisms of the TNF gene protect from progression into sepsis: A study using the new sepsis classification
| Autor: | Evangelos J. Giamarellos-Bourboulis, Michael Bauer, George Dimopoulos, Niki Karampela, Matthias Platzer, Klaus Huse, Theodoros Retsas, Virginia Kolonia, Lazaros-Dimitrios Lazaridis, Eirini Papageorgiou |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Microbiology (medical) Adult Male Single-nucleotide polymorphism Haplotype Tumour necrosis factor alpha Single nucleotide polymorphism Sepsis Polymorphism Single Nucleotide lcsh:Infectious and parasitic diseases 03 medical and health sciences Young Adult Gene Frequency medicine SNP Humans lcsh:RC109-216 Allele Alleles Aged Aged 80 and over business.industry Tumor Necrosis Factor-alpha General Medicine Odds ratio Middle Aged medicine.disease 3. Good health Systemic inflammatory response syndrome 030104 developmental biology Infectious Diseases Haplotypes Immunology Disease Progression Tumor necrosis factor alpha Female business |
| Zdroj: | International journal of infectious diseases, 67:102-106 International Journal of Infectious Diseases, Vol 67, Iss C, Pp 102-106 (2018) |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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