Toll-Like receptor 3 genetic polymorphism in dengue encephalitis
Rajesh Verma1, Atul K Pandey2, Rajarshi Chakraborty1
1Department of Neurology, King George's Medical University, Lucknow, Uttar Pradesh, India.
Context:
Dengue is one of the important vector-borne viral diseases affecting humans with diverse manifestations. Toll-like receptors (TLR) are pattern recognition receptors and play an important role in innate immunity against microbes. TLR3 plays a critical role in controlling the innate immune response mediated by flaviviruses such as dengue.
Aim:
We attempted to study the susceptibility of single nucleotide polymorphism of the TLR3 gene in dengue encephalitis (DE) patients and determine the association in terms of genotype, allele, and haplotype distribution along with the clinical outcome.
Settings And Design:
It was a case-controlled observational study in a tertiary care hospital.
Methods And Material:
We investigated the single nucleotide polymorphism in the TLR3 Leu412Phe gene using real-time polymerase chain reaction in 29 cases of DE and compared them with equal number of age- and sex-matched dengue patients without neurological features.
Statistical Analysis Used:
The genotype and allele frequencies were compared using a two-sided Chi-square or Fisher's exact test.
Results:
The findings revealed that the genotypic distribution of TLR3 Leu412Phe polymorphism for the mutant genotype Phe/Phe (TT) demonstrated increased association of DE (31.03% vs 6.8%, P 0.019, odds ratio 6.075, 95% confidence interval 1.181-31.245). However, the number of heterozygous (H) genotype (Leu/Phe-CT) and mutant Phe allele (T) did not show any statistically significant association. TLR3 gene polymorphism did not show any correlation with mortality outcome at 1 month.
Conclusion:
The presence of mutant TLR3 Leu412Phe polymorphism may confer the propensity to have DE in patients with dengue infection in the Indian population. TLR3 polymorphism did not affect mortality outcome at 1 month.
Insights
The Toll-like receptor 3 (TLR3) Leu412Phe polymorphism is associated with an increased risk of dengue encephalitis. This TLR3 gene variant did not impact mortality outcomes in dengue patients.
Area of Science:
- Immunology
- Genetics
- Infectious Diseases
Background:
- Dengue is a significant vector-borne viral illness with varied human manifestations.
- Toll-like receptors (TLRs) are crucial for innate immunity against pathogens.
- TLR3 plays a key role in the immune response to flaviviruses like dengue.
Purpose of the Study:
- To investigate the association between TLR3 gene single nucleotide polymorphism (SNP) and dengue encephalitis (DE).
- To analyze genotype, allele, and haplotype distributions of TLR3 Leu412Phe polymorphism in DE patients.
- To determine the correlation between TLR3 polymorphism and clinical outcomes, including mortality.
Main Methods:
- A case-controlled observational study was conducted.
- Real-time polymerase chain reaction (PCR) was used to genotype the TLR3 Leu412Phe SNP.
- 29 DE patients were compared with 29 age- and sex-matched dengue patients without neurological complications.
Main Results:
- The mutant genotype Phe/Phe (TT) of TLR3 Leu412Phe polymorphism showed a significant association with DE (31.03% vs 6.8%, P=0.019).
- No statistically significant association was found for the heterozygous genotype (Leu/Phe-CT) or the mutant Phe allele (T).
- TLR3 gene polymorphism did not correlate with 1-month mortality outcomes.
Conclusions:
- The mutant TLR3 Leu412Phe polymorphism may increase susceptibility to DE in dengue-infected individuals within the Indian population.
- TLR3 polymorphism does not appear to influence mortality at one month post-infection.
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