Dataset Information

Tumor necrosis factor alpha gene polymorphism contributes to pulmonary tuberculosis susceptibility: evidence from a meta-analysis.

ABSTRACT: This study is to estimate the association between polymorphisms in the tumor necrosis factor alpha (TNF-?) gene and pulmonary tuberculosis susceptibility (pTB). Studies were identified by searching PubMed and ISI web of Knowledge. The strength of association between the TNF-? gene and pTB susceptibility was assessed by odds ratios. Totals of 18 studies including 2, 735 cases and 3, 177 controls were identified referring to four single-nucleotide polymorphisms: -308G>A, -863C>A, -857C>T and -238G>A. The significantly associations were found between -308G>A (Dominant model: OR 0.53, 95% CI 0.35-0.81, P=0.004; Homozygote model: OR 0.51, 95% CI 0.33-0.78, P=0.002), -238G>A (Dominant model: OR 0.33, 95% CI 0.18-0.57, P<0.001) and pTB susceptibility. The results showed that the variant genotype of TNF-? -308G>A was protective in pooled groups of patients with pTB in the dominant genetic model (OR 0.16, 95% CI 0.06-0.39, P<0.001), the homozygote comparison (OR 0.14, 95% CI 0.06-0.36, P<0.001) in African, while that was with -238G>A in the dominant genetic model (OR 0.31, 95% CI 0.18-0.56, P<0.001) in Asian. Our meta-analysis suggest TNF-? -308G>A and -238G>A polymorphisms increases the risk of pTB susceptibility regardless of ethnicity and HIV statue. In Asian population, the significantly association with pTB is TNF-? -238G>A, while TNF-? -308G>A is in African population.

SUBMITTER: Yi YX

PROVIDER: S-EPMC4723837 | biostudies-other | 2015

REPOSITORIES: biostudies-other

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Tumor necrosis factor alpha gene polymorphism contributes to pulmonary tuberculosis susceptibility: evidence from a meta-analysis.

Yi Yong-Xiang YX Han Jian-Bo JB Zhao Liang L Fang Yuan Y Zhang Yu-Feng YF Zhou Guang-Yao GY

International journal of clinical and experimental medicine 20151115 11

This study is to estimate the association between polymorphisms in the tumor necrosis factor alpha (TNF-α) gene and pulmonary tuberculosis susceptibility (pTB). Studies were identified by searching PubMed and ISI web of Knowledge. The strength of association between the TNF-α gene and pTB susceptibility was assessed by odds ratios. Totals of 18 studies including 2, 735 cases and 3, 177 controls were identified referring to four single-nucleotide polymorphisms: -308G>A, -863C>A, -857C>T and -238G ...[more]

PMID: 26884992

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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 gene polymorphism contributes to pulmonary tuberculosis susceptibility: evidence from a meta-analysis.

Publications

Tumor necrosis factor alpha gene polymorphism contributes to pulmonary tuberculosis susceptibility: evidence from a meta-analysis.

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