Analysis of TLR4 (Asp299Gly and Thr399Ile) gene polymorphisms and mRNA level in patients with dengue infection: A case-control study.
Dengue is a systemic viral infection that spreads to humans by the bite of infected Aedes mosquitoes. The secreted NS1 protein of dengue virus activates macrophages and human PBMCs via TLR4 and induce the release of pro-inflammatory cytokines which is responsible for the pathogenesis of disease. Mutations in TLR4 gene have been associated with the increased susceptibility to many viral, bacterial and parasitic diseases.



To study the impact of TLR4 Asp299Gly (rs4986790) and Thr399Ile (rs4986791) gene polymorphisms with susceptibility to dengue infection.



A total of 120 dengue infected (57; DHF/DSS and 63; DF) and 200 healthy controls were included in the study. TLR4 Asp299Gly and Thr399Ile gene polymorphisms was studied by PCR-RFLP. Expression of TLR4 mRNA was evaluated by rRT-PCR.



Individuals with heterozygous genotype for TLR4 Asp299Gly and Thr399Ile polymorphisms had increased susceptibility to dengue infection (OR-1.70, 95% CI=1.01-2.86 P=0.042 and OR-2.17, 95% CI=1.10-4.28, P=0.024, respectively). The frequency of Gly and Ile alleles were higher in dengue patients as compared to controls (OR-1.67, 95% CI=1.05-2.64, P=0.029 and OR-2.20, 95% CI=1.19-4.07, P=0.011, respectively). IIe/Gly haplotype was associated with the risk of the disease when compared with controls (OR=3.15, 95% CI=1.09-9.09, P=0.035). The mRNA expression was higher in DF when compared with DHF/DSS and controls (P=0.040 and 0.009, respectively).



A higher expression of TLR4 mRNA was associated with DF. The TLR4 Asp299Gly and Thr399Ile gene polymorphisms were associated with the susceptibility of dengue infection probably by altering the immune response.
Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, (U.P), 226014, India; Amity Institute of Biotechnology, Amity University, Lucknow, (U.P), 226028, India.
Swati
S
Sharma
Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, (U.P), 226014, India.
Satyendra K
SK
Singh
Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, (U.P), 226014, India; Amity Institute of Biotechnology, Amity University, Lucknow, (U.P), 226028, India.
Kavita
K
Kakkar
Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, (U.P), 226014, India.
Nikky
N
Nyari
Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, (U.P), 226014, India. Electronic address: tndhole@gmail.com.
Tapan N
TN
Dhole
Department of Hematology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, (U.P), 226014, India.
Rajesh
R
Kashyap
Amity Institute of Biotechnology, Amity University, Lucknow, (U.P), 226028, India.
Saba
S
Hasan
D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution; D016022:Case-Control Studies; D003715:Dengue / Q000235:genetics* / Q000276:immunology / Q000821:virology; D003716:Dengue Virus / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics* / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000235:genetics* / Q000276:immunology; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism
C082515:NS1 protein, dengue-1 virus; D012333:RNA, Messenger; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D017361:Viral Nonstructural Proteins
Dengue; Genetic susceptibility; Haplotypes; Humans; Polymorphism