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Association of tumor necrosis factor ? genetic polymorphism and sepsis susceptibility.

ABSTRACT: The association of the tumor necrosis factor ? (TNF-?) Nco1 genetic polymorphism with susceptibility to sepsis was evaluated in 60 consecutive patients diagnosed with sepsis and in 148 healthy blood donors. Genomic DNA was extracted from peripheral blood cells and a 782 base-pair fragment of the TNF-? gene was amplified by PCR. The PCR products were subjected to Nco1 restriction digestion and analysed by restriction fragment length polymorphism analysis. Tumor necrosis factor ? (TNF-?) and the C-reactive protein (CRP) serum levels were also determined by ELISA and nephelometry, respectively. Among the septic patients, the allelic frequencies of TNFB1 and TNFB2 were 0.2833 and 0.7166, respectively, and they differed from those observed in the blood donors (p=0.0282). The TNFB2 allele frequency was higher in the septic patients than in the blood donors [odds ratio=1.65 (CI 95% 1.02-2.69), p=0.0315]. The TNF-? and CRP serum levels and the APACHE II and SOFA clinical scores did not differ in the patients with the TNFB1 or TNFB2 alleles (p>0.05). The results suggest that the TNFB2 allele is associated with susceptibility to sepsis, but it was not found to be associated with the immunological and clinical biomarkers of the disease.

SUBMITTER: Delongui F

PROVIDER: S-EPMC3440649 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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Association of tumor necrosis factor β genetic polymorphism and sepsis susceptibility.

Delongui Francieli F Carvalho Grion Cíntia Magalhães CM Ehara Watanabe Maria Angelica MA Morimoto Helena Kaminami HK Bonametti Ana Maria AM Maeda Oda Julie Massayo JM Kallaur Ana Paula AP Matsuo Tiemi T Reiche Edna Maria EM

Experimental and therapeutic medicine 20110120 2

The association of the tumor necrosis factor β (TNF-β) Nco1 genetic polymorphism with susceptibility to sepsis was evaluated in 60 consecutive patients diagnosed with sepsis and in 148 healthy blood donors. Genomic DNA was extracted from peripheral blood cells and a 782 base-pair fragment of the TNF-β gene was amplified by PCR. The PCR products were subjected to Nco1 restriction digestion and analysed by restriction fragment length polymorphism analysis. Tumor necrosis factor α (TNF-α) and the C ...[more]

PMID: 22977509

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Project description:To investigate the significance of functional polymorphisms of inflammatory response genes by analysis of a large population of patients, both with and without severe sepsis, and representative of the diverse populations (geographic diversity, physician diversity, clinical treatment diversity) that would be encountered in critical care clinical practice.: Collaborative case-control study conducted from July 2001 to December 2005.A heterogeneous population of patients from 12 U.S. intensive care units represented by the Genetic Predisposition to Severe Sepsis archive.A total of 854 patients with severe sepsis and an equal number of mortality, age, gender, and race-matched patients also admitted to the intensive care unit without evidence of any infection (matched nonseptic controls).We developed assays for six functional single nucleotide polymorphisms present before the first codon of tumor necrosis factor at -308, IL1B at -511, IL6 at -174, IL10 at -819, and CD14 at -159, and in the first intron of LTA (also known as tumor necrosis factor-B) at +252 (LTA[+252]). The Project IMPACT critical care clinical database information management system developed by the Society of Critical Care Medicine and managed by Tri-Analytics and Cerner Corporation was utilized. Template-directed dye-terminator incorporation assay with fluorescence polarization detection was used as a high-throughput genotyping strategy. Fifty-three percent of the patients were male with 87.3% and 6.4% of Caucasian and African American racial types, respectively. Overall mortality was 35.1% in both severe sepsis and matched nonseptic control patients group. Average ages (standard deviation) of the severe sepsis and matched nonseptic control patients were 63.0 (16.05) and 65.0 (15.58) yrs old, respectively. Among the six single nucleotide polymorphisms, LTA (+252) was most overrepresented in the septic patient group (% severe sepsis; AA 45.6: AG 51.1: GG 56.7, p = .005). Furthermore, the genetic risk effect was most pronounced in males, age >60 yrs (p = .005).LTA(+252) may influence predisposition to severe sepsis, a predisposition that is modulated by gender and age. Although the genetic influences can be overwhelmed by both comorbid factors and acute illness in individual cases, population studies suggest that this is an influential biological pathway modulating risk of critical illnesses.

Project description:OBJECTIVE:Several published studies have investigated the association between the -308G/A (rs1800629) polymorphism in the tumor necrosis factor-? (TNF-?) gene and the risk of dilated cardiomyopathy (DCM). However, the TNF-? gene polymorphism has a controversial role in the pathogenesis of DCM among different populations. In the present study, a meta-analysis was performed to resolve this inconsistency. METHODS:Potentially eligible papers reporting an association between the TNF-? rs1800629 polymorphism and DCM susceptibility were searched in 4 databases including PubMed, EMBASE, Chinese Biomedical Database (CBM), and the Cochrane Library up to April 1, 2018. The odds ratio (OR) with its 95% confidence interval (CI) was used to estimate the strength of the associations. Subgroup analysis based on the ethnicity, studies with or without ischemic and valvular DCM was conducted. Publication bias detection was conducted using Begg test. RESULTS:Nine papers detailing case-control studies were included, reporting a total of 1339 DCM cases and 1677 healthy controls. The meta-analysis results indicated that TNF-? rs1800629 was associated with increased DCM susceptibility in the populations studied under the heterozygous model (AG vs GG: OR?=?1.91, 95% CI?=?1.05-3.50, P?=?.035) and dominant model (AG?+?AA vs GG: OR?=?1.87, 95% CI?=?1.01-3.45, P?=?.046). In the subgroup analysis for ethnicity, rs1800629 polymorphism was significantly associated with the susceptibility of DCM for Asians under the 5 models (A vs G: OR?=?2.87, 95% CI?=?1.56-5.30, P?=?.001; AA vs GG: OR?=?3.95, 95% CI?=?1.13-13.82, P?=?0.031; AG vs GG: OR?=?3.8, 95% CI?=?1.57-9.19, P?=?.003; AA vs GG?+?AG: OR?=?2.51, 95% CI?=?1.41-4.49, P?=?.002; AG?+?AA vs GG: OR?=?3.77, 95% CI?=?1.54-9.20, P?=?.004). CONCLUSION:There may be a moderate association between TNF-? rs1800629 polymorphism and DCM susceptibility in the whole populations studied; however, TNF-? rs1800629 polymorphism was significantly associated with the susceptibility of DCM for Asians, which indicates that such associations may be different between ethnicities.

Dataset Information

Association of tumor necrosis factor ? genetic polymorphism and sepsis susceptibility.

Publications

Association of tumor necrosis factor β genetic polymorphism and sepsis susceptibility.

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