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Year : 2020  |  Volume : 68  |  Issue : 1  |  Page : 78--83

The Relationship Between Tumor Necrosis Factor-Alpha (-308G/A, +488G/A, -857C/T, and -1031T/C) Gene Polymorphisms and Risk of Intracerebral Hemorrhage in the North Indian Population: A Hospital-Based Case-Control Study

1 Department of Neurology, All India Institute of Medical Sciences, New Delhi, India
2 Department of Genomics and Molecular Medicine, Institute of Genomics and Integrative Biology, New Delhi, India
3 Department of Neurobiochemistry, All India Institute of Medical Sciences, New Delhi, India

Correspondence Address:
Dr. Kameshwar Prasad
Department of Neurology, Neurosciences Centre, All India Institute of Medical Sciences, Ansari Nagar, New Delhi
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.279665

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Introduction: Genetic factors may play a role in the susceptibility of intracerebral hemorrhage (ICH). The present case-control study hypothesized that genetic polymorphisms in tumor necrosis factor- α (TNF-α) gene may affect the risk of ICH. Materials and Methods: In this study, we investigated the association of four single nucleotide polymorphisms (-308G/A, +488G/A, -857C/T, and -1031T/C) within TNF-α gene promoter and their haplotypes with the risk of ICH in a North Indian population. Genotyping was determined by using the SNaPshot method for 100 ICH patients and 100 age and sex-matched ICH-free controls. Conditional logistic regression analysis with adjusting multiple demographic and risk factor variables was used to calculate the strength of association between TNF-α gene polymorphisms and risk of ICH. Haplotypes were reconstructed using PHASE 2.0, and patterns of linkage disequilibrium (LD) analysis were performed using Haploview version 4.2 software. Results: TNF-α +488G/A gene polymorphism was found to be independently associated with the risk of ICH under dominant [GG + GA vs. AA] (OR = 3.1; 95% CI = 1.2–8.2; P = 0.001) and allelic [G vs. A] (OR = 2.2; 95% CI = 1.2–4.2; P = 0.007) models. However, no significant association between -308G/A, -857C/T, and -1031T/C gene polymorphisms and risk of ICH was observed. Haplotype analysis showed that 308A-488G-857C-1031T and 308G-488A-857T-1031T haplotypes were significantly associated with an increased risk of ICH. Strong LD was observed for + 488G/A and -857C/T TNF-α polymorphisms (D' = 0.72, r2= 0.01). Conclusion: Our findings suggest that the TNF-α +488G/A polymorphism may be an important risk factor for ICH, whereas -308G/A, -857C/T, and -1031T/C gene polymorphisms may not be associated with risk of ICH in North Indian population.


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Online since 20th March '04
Published by Wolters Kluwer - Medknow