| ORIGINAL ARTICLE
|Year : 2020 | Volume
| 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
Pradeep Kumar1, Shubham Misra1, Amit Kumar1, Mohammad Faruq2, Subiah Vivekanandhan3, Achal K Srivastava1, Kameshwar Prasad1
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
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.
Dr. Kameshwar Prasad
Department of Neurology, Neurosciences Centre, All India Institute of Medical Sciences, Ansari Nagar, New Delhi
Source of Support: None, Conflict of Interest: None
[FULL TEXT] [PDF]*