Evaluation of TNF-α genetic polymorphisms as predictors for sepsis susceptibility and progression
Abstract Background The goal of the study was to evaluate a potential role for tumor necrosis factor alpha (TNF-α) genetic variability as biomarker in sepsis. In particular, we aimed to determine if single nucleotide polymorphisms (SNPs) of TNF-α gene are associated with sepsis in terms of risk, sev...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2020-03-01
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| Series: | BMC Infectious Diseases |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12879-020-4910-6 |
| _version_ | 1818505597950099456 |
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| author | Anca Meda Georgescu Claudia Banescu Razvan Azamfirei Adina Hutanu Valeriu Moldovan Iudita Badea Septimiu Voidazan Minodora Dobreanu Ioana Raluca Chirtes Leonard Azamfirei |
| author_facet | Anca Meda Georgescu Claudia Banescu Razvan Azamfirei Adina Hutanu Valeriu Moldovan Iudita Badea Septimiu Voidazan Minodora Dobreanu Ioana Raluca Chirtes Leonard Azamfirei |
| author_sort | Anca Meda Georgescu |
| collection | DOAJ |
| description | Abstract Background The goal of the study was to evaluate a potential role for tumor necrosis factor alpha (TNF-α) genetic variability as biomarker in sepsis. In particular, we aimed to determine if single nucleotide polymorphisms (SNPs) of TNF-α gene are associated with sepsis in terms of risk, severity and outcome. Methods We performed a prospective study on 163 adult critically ill septic patients (septic shock 65, sepsis 98, further divided in 40 survivors and 123 deceased) and 232 healthy controls. Genotyping of TNF-α SNPs (-308G/A, -238G/A, -376G/A and +489G/A) was performed for all patients and controls and plasma cytokine levels were measured during the first 24 h after sepsis onset. Results TNF-α +489G/A A-allele carriage was associated with significantly lower risk of developing sepsis and sepsis shock (AA+AG vs GG: OR = 0.53; p = 0.004; 95% CI = 0.34–0.82 and OR = 0.39; p = 0.003; 95% CI = 0.21–0.74, respectively) but not with sepsis-related outcomes. There was no significant association between any of the other TNF-α promoter SNPs, or their haplotype frequencies and sepsis or septic shock risk. Circulating TNF-α levels were higher in septic shock; they were not correlated with SNP genotype distribution; GG homozygosity for each polymorphism was correlated with higher TNF-α levels in septic shock. Conclusions TNF-α +489G/A SNP A-allele carriage may confer protection against sepsis and septic shock development but apparently does not influence sepsis-related mortality. Promoter TNF-α SNPs did not affect transcription and were not associated with distinct sepsis, septic shock risk or outcomes. |
| first_indexed | 2024-12-10T21:53:04Z |
| format | Article |
| id | doaj.art-9bd75e4a023147339dbbe4df45299ded |
| institution | Directory Open Access Journal |
| issn | 1471-2334 |
| language | English |
| last_indexed | 2024-12-10T21:53:04Z |
| publishDate | 2020-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Infectious Diseases |
| spelling | doaj.art-9bd75e4a023147339dbbe4df45299ded2022-12-22T01:32:08ZengBMCBMC Infectious Diseases1471-23342020-03-0120111110.1186/s12879-020-4910-6Evaluation of TNF-α genetic polymorphisms as predictors for sepsis susceptibility and progressionAnca Meda Georgescu0Claudia Banescu1Razvan Azamfirei2Adina Hutanu3Valeriu Moldovan4Iudita Badea5Septimiu Voidazan6Minodora Dobreanu7Ioana Raluca Chirtes8Leonard Azamfirei9Infectious Diseases Clinic, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu MuresGenetics Laboratory, Center for Advanced Medical and Pharmaceutical Research, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu MuresJohns Hopkins School of Medicine, Johns Hopkins UniversityImmunology Laboratory, Center for Advanced Medical and Pharmaceutical Research, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu MuresGenetics Laboratory, Center for Advanced Medical and Pharmaceutical Research, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu MuresDepartment of Anesthesiology and Intensive Care, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu MuresDepartment of Epidemiology, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu MuresImmunology Laboratory, Center for Advanced Medical and Pharmaceutical Research, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu MuresInfectious Diseases Clinic, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu MuresDepartment of Anesthesiology and Intensive Care, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu MuresAbstract Background The goal of the study was to evaluate a potential role for tumor necrosis factor alpha (TNF-α) genetic variability as biomarker in sepsis. In particular, we aimed to determine if single nucleotide polymorphisms (SNPs) of TNF-α gene are associated with sepsis in terms of risk, severity and outcome. Methods We performed a prospective study on 163 adult critically ill septic patients (septic shock 65, sepsis 98, further divided in 40 survivors and 123 deceased) and 232 healthy controls. Genotyping of TNF-α SNPs (-308G/A, -238G/A, -376G/A and +489G/A) was performed for all patients and controls and plasma cytokine levels were measured during the first 24 h after sepsis onset. Results TNF-α +489G/A A-allele carriage was associated with significantly lower risk of developing sepsis and sepsis shock (AA+AG vs GG: OR = 0.53; p = 0.004; 95% CI = 0.34–0.82 and OR = 0.39; p = 0.003; 95% CI = 0.21–0.74, respectively) but not with sepsis-related outcomes. There was no significant association between any of the other TNF-α promoter SNPs, or their haplotype frequencies and sepsis or septic shock risk. Circulating TNF-α levels were higher in septic shock; they were not correlated with SNP genotype distribution; GG homozygosity for each polymorphism was correlated with higher TNF-α levels in septic shock. Conclusions TNF-α +489G/A SNP A-allele carriage may confer protection against sepsis and septic shock development but apparently does not influence sepsis-related mortality. Promoter TNF-α SNPs did not affect transcription and were not associated with distinct sepsis, septic shock risk or outcomes.http://link.springer.com/article/10.1186/s12879-020-4910-6TNF-αSingle nucleotide polymorphismSepsis |
| spellingShingle | Anca Meda Georgescu Claudia Banescu Razvan Azamfirei Adina Hutanu Valeriu Moldovan Iudita Badea Septimiu Voidazan Minodora Dobreanu Ioana Raluca Chirtes Leonard Azamfirei Evaluation of TNF-α genetic polymorphisms as predictors for sepsis susceptibility and progression BMC Infectious Diseases TNF-α Single nucleotide polymorphism Sepsis |
| title | Evaluation of TNF-α genetic polymorphisms as predictors for sepsis susceptibility and progression |
| title_full | Evaluation of TNF-α genetic polymorphisms as predictors for sepsis susceptibility and progression |
| title_fullStr | Evaluation of TNF-α genetic polymorphisms as predictors for sepsis susceptibility and progression |
| title_full_unstemmed | Evaluation of TNF-α genetic polymorphisms as predictors for sepsis susceptibility and progression |
| title_short | Evaluation of TNF-α genetic polymorphisms as predictors for sepsis susceptibility and progression |
| title_sort | evaluation of tnf α genetic polymorphisms as predictors for sepsis susceptibility and progression |
| topic | TNF-α Single nucleotide polymorphism Sepsis |
| url | http://link.springer.com/article/10.1186/s12879-020-4910-6 |
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