Dataset Information

Tumor necrosis factor alpha promoter polymorphism and severity of acute kidney injury.

ABSTRACT: Tumor necrosis factor-alpha is a proinflammatory cytokine that has been implicated in the pathobiology of acute kidney injury (AKI).We explored the association of a functional polymorphism in the promoter region (rs1800629) of the TNFA gene with severity of AKI, as defined by level of glomerular filtration (serum cystatin C and creatinine) and tubular injury (urinary NAG, KIM-1, ?-GST, and ?-GST) markers, in 262 hospitalized adults.In unadjusted analyses, compared with the GG genotype, the TNFA GA and AA genotype groups tended to have higher enrollment (p = 0.08), peak (p = 0.004), and discharge (p = 0.004) serum creatinine levels, and the AA genotype tended to have a higher enrollment serum cystatin C level (p = 0.04). Compared with the GG genotype, the TNFA GA and AA genotype groups tended to have a higher urinary KIM-1 level (p = 0.03), and the AA genotype group tended to have a higher urinary ?-GST level (p = 0.03). After adjustment for sex, race, age, baseline estimated glomerular filtration rate, sepsis, and dialysis requirement, compared with the GG genotype, the TNFA minor A-allele group had a higher peak serum creatinine of 1.03 mg/dl (0.43, 1.63; p = 0.001) and a higher urinary KIM-1 (relative ratio: 1.73; 95% CI: 1.16, 2.59; p = 0.008). The TNFA minor A-allele group also had a higher Multiple Organ Failure score of 0.26 (95% CI: 0.03, 0.49; p = 0.024) after adjustment for sex, race, age, and sepsis.The TNFA rs1800629 gene polymorphism is associated with markers of kidney disease severity and distant organ dysfunction among patients with AKI. Larger studies are needed to confirm these relationships.

SUBMITTER: Susantitaphong P

PROVIDER: S-EPMC4959276 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Tumor necrosis factor alpha promoter polymorphism and severity of acute kidney injury.

Susantitaphong Paweena P Perianayagam Mary C MC Tighiouart Hocine H Liangos Orfeas O Bonventre Joseph V JV Jaber Bertrand L BL

Nephron. Clinical practice 20130621 1-2

<h4>Background</h4>Tumor necrosis factor-alpha is a proinflammatory cytokine that has been implicated in the pathobiology of acute kidney injury (AKI).<h4>Methods</h4>We explored the association of a functional polymorphism in the promoter region (rs1800629) of the TNFA gene with severity of AKI, as defined by level of glomerular filtration (serum cystatin C and creatinine) and tubular injury (urinary NAG, KIM-1, α-GST, and π-GST) markers, in 262 hospitalized adults.<h4>Results</h4>In unadjusted ...[more]

PMID: 23796916

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Project description:BackgroundReported associations between Tumor Necrosis Factor-alpha (TNFA) and the postprandial triacylglycerol (TAG) response have been inconsistent, which could be due to variations in the TNFA gene, meal fat composition or participant's body weight. Hence, we investigated the association of TNFA polymorphism (-308G → A) with body mass index (BMI) and postprandial lipaemia and also determined the impact of BMI on the association of the polymorphism with postprandial lipaemia.MethodsThe study participants (n = 230) underwent a sequential meal postprandial study. Blood samples were taken at regular intervals after a test breakfast (t = 0, 49 g fat) and lunch (t =330 min, 29 g fat) to measure fasting and postprandial lipids, glucose and insulin. The Metabolic Challenge Study (MECHE) comprising 67 Irish participants who underwent a 54 g fat oral lipid tolerance test was used as a replication cohort. The impact of genotype on postprandial responses was determined using general linear model with adjustment for potential confounders.ResultsThe -308G → A polymorphism showed a significant association with BMI (P = 0.03) and fasting glucose (P = 0.006), where the polymorphism explained 13 % of the variation in the fasting glucose. A 30 % higher incremental area under the curve (IAUC) was observed for the postprandial TAG response in the GG homozygotes than A-allele carriers (P = 0.004) and the genotype explained 19 % of the variation in the IAUC. There was a non-significant trend in the impact of BMI on the association of the genotype with TAG IAUC (P = 0.09). These results were not statistically significant in the MECHE cohort, which could be due to the differences in the sample size, meal composition, baseline lipid profile, allelic diversity and postprandial characterisation of participants across the two cohorts.ConclusionsOur findings suggest that TNFA -308G → A polymorphism may be an important candidate for BMI, fasting glucose and postprandial TAG response. Further studies are required to investigate the mechanistic effects of the polymorphism on glucose and TAG metabolism, and determine whether BMI is an important variable which should be considered in the design of future studies.Trial registrationNCT01172951 .

Project description:The multifactorial pathogenesis of severe malaria is partly attributed to host genes, such as those encoding cytokines involved in complex inflammatory reactions, namely tumor necrosis factor-alpha (TNF-α). However, the relationship between TNF-α -308G >A gene polymorphism (rs1800629) and the severity of Plasmodium falciparum (P. falciparum) malaria remains unclear, which prompts a meta-analysis to obtain more precise estimates. The present meta-analysis aimed to better understand this correlation and provide insight into its association in populations with different ethnicities. Literature search outcomes included eight eligible articles in which TNF-α -308G >A polymorphism was determined in uncomplicated malaria (UM) and severe malaria (SM) of P. falciparum as represented in the case and control groups. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated in standard homozygous, recessive, dominant, and codominant genetic models. Subgroup analysis was based on ethnicity, i.e., Africans and Asians. The analyses included overall and the modified outcomes; the latter was obtained without the studies that deviated from the Hardy-Weinberg Equilibrium. The significant data also underwent sensitivity treatment but not publication bias tests because the number of studies was less than ten. Interaction tests were applied to differential outcomes between the subgroups. Overall and HWE-compliant analyses showed no significant association between the TNF-α -308G >A polymorphism and susceptibility to P. falciparum SM (ORs = 1.10-1.52, 95%CIs = 0.68-2.79; Pa = 0.24-0.68). Stratification by ethnicity revealed that two significant associations were found only in the Asians favoring SM for dominant (OR = 1.95, 95% CI = 1.06-3.61, Pa = 0.03) and codominant (OR = 1.83, 95% CI = 1.15-2.92, Pa = 0.01) under the random-effects model, but not among the African populations. The two significant Asian associations were improved with a test of interaction with P-value of0.02-0.03. The significant core outcomes were robust. Results of the meta-analysis suggest that TNF-α -308G >A polymorphism might affect the risk of P. falciparum SM, particularly in individuals of Asian descent. This supports ethnicity as one of the dependent factors of the TNF-α -308G >A association with the clinical severity of malaria. Further large and well-designed genetic studies are needed to confirm this conclusion.

Dataset Information

Tumor necrosis factor alpha promoter polymorphism and severity of acute kidney injury.

Publications

Tumor necrosis factor alpha promoter polymorphism and severity of acute kidney injury.

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