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Transforming growth factor-?1 (C509T, G800A, and T869C) gene polymorphisms and risk of ischemic stroke in North Indian population: A hospital-based case-control study.

ABSTRACT: BACKGROUND:Transforming growth factor-beta 1 (TGF-?1) is a multifunctional pleiotropic cytokine involved in inflammation and pathogenesis of cerebrovascular diseases. There is limited information on the association between variations within the TGF-?1 gene polymorphisms and risk of ischemic stroke (IS). The aim of this study was to investigate the association of the TGF-?1 gene (C509T, G800A, and T869C) polymorphisms, and their haplotypes with the risk of IS in North Indian population. METHODS:A total of 250 IS patients and 250 age- and sex-matched controls were studied. IS was classified using the Trial of Org 10172 in Acute Stroke Treatment classification. Conditional logistic regression analysis was used to calculate the strength of association between TGF-?1 gene polymorphisms and risk of IS. Genotyping was performed using SNaPshot method. RESULTS:Hypertension, diabetes, dyslipidemia, alcohol, smoking, family history of stroke, sedentary lifestyle, and low socioeconomic status were found to be associated with the risk of IS. The distribution of C509T, G800A and T869C genotypes was consistent with Hardy-Weinberg Equilibrium in the IS and control groups. Adjusted conditional logistic regression analysis showed a significant association of TGF-?1 C509T (odds ratio [OR], 2.1; 95% CI; 1.2-3.8; P = 0.006), G800A (OR, 4.4; 95% CI; 2.1-9.3; P < 0.001) and T869C (OR, 2.6; 95% CI; 1.5-4.5; P = 0.001) with the risk of IS under dominant model. Haplotype analysis showed that C509-A800-T869 and T509-G800-C869 haplotypes were significantly associated with the increased risk of IS. C509T and T869C were in strong linkage disequilibrium (D' =0.51, r2 = 0.23). CONCLUSION:Our results suggest that TGF-?1 polymorphisms and their haplotypes are significantly associated with the risk of IS in North Indian population.

SUBMITTER: Kumar P

PROVIDER: S-EPMC5341267 | biostudies-literature | 2017 Jan-Mar

REPOSITORIES: biostudies-literature

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Transforming growth factor-β1 (C509T, G800A, and T869C) gene polymorphisms and risk of ischemic stroke in North Indian population: A hospital-based case-control study.

Kumar Pradeep P Misra Shubham S Kumar Amit A Faruq Mohammad M Shakya Sunil S Vardhan Gyan G Vivekanandhan Subiah S Srivastava Achal Kumar AK Prasad Kameshwar K

Annals of Indian Academy of Neurology 20170101 1

<h4>Background</h4>Transforming growth factor-beta 1 (TGF-β1) is a multifunctional pleiotropic cytokine involved in inflammation and pathogenesis of cerebrovascular diseases. There is limited information on the association between variations within the TGF-β1 gene polymorphisms and risk of ischemic stroke (IS). The aim of this study was to investigate the association of the TGF-β1 gene (C509T, G800A, and T869C) polymorphisms, and their haplotypes with the risk of IS in North Indian population.<h ...[more]

PMID: 28298836

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Project description:ObjectiveTo explore the association between transforming growth factor-beta1 (TGF-?1) T869C polymorphism and risk of ischemic stroke (IS) by performing a meta-analysis based on published articles.MethodsSystematic electronic searches of PubMed, Science Direct, BIOSIS Previews, Chinese Biomedical Database, Chinese National Knowledge Infrastructure, and WANFANG Database were performed. The strength of the association was calculated by pooled odds ratios (ORs) with 95% confidence intervals (95%CIs). Subgroup analysis was conducted to explore potential sources of heterogeneity. Sensitivity analysis was performed to elucidate the stability of the outcomes. Publication bias was evaluated by Begg's funnel plot and Egger's test.ResultsA total of 6 studies involving 1701 cases were included. The overall estimates did not show any significant association between TGF-?1 T869C polymorphism and risk of IS under all genetic models (C vs. T: OR?=?1.08,95%CI?=?0.88-1.32; CC vs. TT:OR?=?1.17,95%CI?=?0.79-1.72; CT vs. TT: OR?=?0.91, 95%CI?=?0.68-1.22; CC+CT vs. TT: OR?=?0.99, 95%CI?=?0.73-1.35; CC vs. CT+TT: OR?=?1.23, 95%CI?=?0.95-1.59). Similar lacking associations were observed in subgroup analysis based on ethnicity and source of controls. When stratified by study design, significant increased association of IS risk was found in cohort studies under genetic models except recessive model(C vs. T: OR?=?1.18, 95%CI?=?1.05-1.32; CC vs. TT: OR?=?1.40, 95%CI?=?1.10-1.77; CT vs. TT: OR?=?1.23, 95%CI?=?1.02-1.49; CC+CT vs. TT: OR?=?1.27, 95%CI?=?1.03-1.57; CC vs. CT+TT, OR?=?1.21, 95%CI?=?0.99-1.47), whereas in case-control studies a significant decreased risk was detected under heterozygote comparison(CT vs. CC: OR?=?0.72, 95%CI?=?0.57-0.92). However, after correction for multiple testing, the associations were observed to be null significant in both cohort and case-control subgroups among all genetic models.ConclusionThis meta-analysis suggested that current epidemiological studies of TGF-?1 T869C polymorphism are too inconsistent to draw a conclusion on the association with IS susceptibility. Given the small sample size and remarkable between-study heterogeneity, further well-designed prospective large-scale studies are warranted.

Project description:BackgroundGenetic factors may play a role in the susceptibility of Ischemic stroke (IS). Previous studies have shown that Tumour necrosis factor-α (TNF-α) gene polymorphisms were associated with the risk of IS in multiple ethnicities. The present case-control study tested the hypothesis that genetic polymorphisms of the TNF-α gene may affect the risk of IS in North Indian population. We investigated the association of four single nucleotide polymorphisms (- 308G/A, + 488G/A, - 857C/T and -1031 T/C) within TNF-α gene promoter and their haplotypes with the risk of IS.MethodsIS was classified using the Trial of Org 10,172 in Acute Stroke Treatment (TOAST) classification. Genotyping was performed for 250 IS patients and 250 age- and sex-matched IS free controls by using SNaPshot technique. Multivariate logistic regression was used to control the confounding effects of demographic and risk factor variables. Haplotype analyses were done by using PHASE software and Linkage disequilibrium (LD) analyses were done by using Haploview version 4.2 software.ResultsAn independent association between TNF-α + 488G/A (OR = 2.59; 95%CI 1.46 to 4.60; p = 0.001) and -857C/T (OR = 1.77; 95%CI 1.01 to 3.11; p < 0.04) and risk of IS was observed under dominant model. However, no significant association between -308G/A and -1031 T/C gene polymorphisms and risk of IS was observed. Haplotype analysis showed that A308-G488-C857-T1031 haplotypes were significantly associated with the increased risk of IS [OR = 1.66; 95%CI 1.02 to 2.71; p = 0.003]. Strong linkage disequilibrium (LD) was observed for + 488G/A and -857C/T (D' = 0.41, r(2) = 0.004).ConclusionsTwo SNPs (+ 488G/A and -857C/T) of TNF-α gene and their haplotypes are significantly associated with the risk of IS in the population enrolled from North India. Our findings indicate that polymorphisms and haplotypes of TNF-α gene may be used as a genetic marker for identifying individuals at increased risk for developing IS.

Project description:BACKGROUND AND PURPOSE:Stroke is a multifactorial disease influenced by both genetic and environmental factors. The aim of this case-control study was to determine the association between ?-fibrinogen C148T (rs1800787) gene polymorphism and susceptibility to ischemic stroke (IS) in a North Indian population. METHODS:In the present case-control study, genotyping was performed using the PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) method on 250 IS patients and 250 age- and sex-matched controls. Frequency distributions of genotypes and alleles were compared between the cases and controls by conditional logistic regression. RESULTS:Hypertension, diabetes, dyslipidemia, low socioeconomic status, and family history of stroke were found to be independent risk factors for IS. The mean age of the cases and controls was 52.83 ± 12.59 and 50.97 ± 12.70 years, respectively. Multivariate logistic regression analysis showed an independent association between ?-fibrinogen C148T (rs1800787) polymorphism and risk of IS in dominant (OR = 2.19; 95% CI 1.23-3.90; p = 0.007) and allelic (OR = 1.66; 95% CI 1.19-2.33; p = 0.002) models. Based on the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification, an independent association of small vessel disease with risk of IS was observed in the dominant (OR = 2.09; 95% CI 1.10-3.96; p = 0.02) and allelic (OR = 1.75; 95% CI 1.12-2.75; p = 0.01) models, and a significant association of cardioembolic stroke with risk of IS was seen in the allelic model (OR = 2.11; 95% CI 1.07-4.17; p = 0.02). All the genotype frequencies observed were in accordance with Hardy-Weinberg equilibrium in both cases and controls. CONCLUSION:The findings of the present study suggest that polymorphism in the C148T position of the ?-fibrinogen gene might be a risk factor for IS mainly for the small vessel disease stroke subtype in a North Indian population. Further, large prospective studies are required to confirm these findings.

Dataset Information

Transforming growth factor-?1 (C509T, G800A, and T869C) gene polymorphisms and risk of ischemic stroke in North Indian population: A hospital-based case-control study.

Publications

Transforming growth factor-β1 (C509T, G800A, and T869C) gene polymorphisms and risk of ischemic stroke in North Indian population: A hospital-based case-control study.

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