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Promoter polymorphism of TNF-α (rs1800629) is associated with ischemic stroke susceptibility in a southern Thai population.

ABSTRACT: Stroke represents the leading cause of disability and mortality amongst the elderly worldwide. Multiple risk factors, including both genetic and non-genetic components, as well as their interactions, are proposed as etiological factors involved in the development of ischemic stroke (IS). Promoter polymorphisms of the IL-6-174G/C (rs1800795) and TNF-α-308G/A (rs1800629) genes have been considered as predictive risk factors of IS; however, these have not yet been evaluated in a Thai population. The aims of this study were to investigate the association of IL-6-174G/C and TNF-α-308G/A polymorphisms with IS. Genomic DNA from 200 patients with IS and 200 controls were genotyped for IL-6-174G/C and TNF-α-308G/A polymorphisms using TaqMan™ SNP genotyping and quantitative PCR-high resolution melting analysis, respectively. It was found that the TNF-α-308 A allele was significantly associated with an increased risk of IS development compared with the G allele [odds ratio (OR)=2.044; 95% CI=1.154-3.620; P=0.014]. Moreover, the IS risk was significantly higher in the presence of TNF-α-308 GA or AA genotypes compared with that in the presence of GG genotypes with a dominant inheritance (OR=1.971; 95% CI=1.080-3.599; P=0.027). However, there was no association between IL-6-174G/C and the risk of IS development. The interaction study demonstrated that IL-6-174 GG and TNF-α-308 GG genotypes enhanced IS susceptibility when combined with hypertension, hyperlipidemia and alcohol consumption. Hypertensive and hyperlipidemic subjects with the TNF-α-308 GA and AA genotypes were more likely to develop IS compared with those who did not have these two conditions and had the GG genotype. In a matched study design (1:1), the IL-6-174 GC genotype was associated with higher IL-6 levels in the control group. Collectively, the present results highlight the utility of the TNF-α-308G/A polymorphism as a predictive genetic risk factor for development of IS.

SUBMITTER: Kamdee K

PROVIDER: S-EPMC8329996 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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.

Project description:To investigate the association between the susceptibility to cervical cancer and the single nucleotide polymorphisms of 5 tumor necrosis factor-α promoter genes (rs361525, rs1800629, rs1800750, rs1799964, and rs673) in Chinese women. A total of 946 peripheral blood samples were collected from women of Han Ethnicity in Shandong province. Of them, 452 were diagnosed with cervical squamous cell carcinomas. The study also included a control group of 494 healthy women. The targeted single nucleotide polymorphisms were analyzed by TaqMan probe method. (1) The rate of high-risk subtype human papillomavirus infection in exfoliated cervical epithelial cells was significantly higher in patients with cervical cancer than the control group (91.4% vs 10.3%, P < .01). The rate of human papillomavirus infection was lower in patients with carcinoma in situ than those with invasive carcinoma (77.9% vs 95.4%, P < .01). (2) There was a significant difference for rs361525 genotype (CC/CT/TT) between the control, carcinoma in situ, and invasive carcinoma groups ( P < .001). Both rs1800629 and rs1799964 genotypes (both GG/GA/AA) were also different between these groups ( P < .001 and P < .001). (3) The allele frequencies of rs361525, rs1800629, and rs1799964 were significantly correlated with the diagnosis of cervical cancer. The frequency of T allele in rs361525 was significantly higher for cervical cancer group (10.8%) than control group (3.8%; odds ratio = 3.04, 95% confidence interval = 1.76-5.25, P < .01). The frequency of A allele in rs1800629 was significantly higher for cervical cancer (29.9%) than control group (14.2%; odds ratio = 2.58, 95% confidence interval = 1.87-3.56, P < .01). The frequency of A allele in rs1799964 was also higher for cervical cancer group (38.3%) than control group (16.4%; odds ratio = 1.43, 95% confidence interval = 1.07-1.91, P < .05). The rs361525, rs1800629, and rs17999645 were significantly correlated with the diagnosis of cervical cancer.

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Promoter polymorphism of TNF-α (rs1800629) is associated with ischemic stroke susceptibility in a southern Thai population.

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