Toll-like receptor-3 gene polymorphism in patients with Japanese encephalitis

Biyani, Sumant; Garg, Ravindra Kumar; Jain, Amita; Malhotra, Hardeep Singh; Kumar, Rashmi; Prakash, Shantanu; Verma, Rajesh; Sharma, Praveen

doi:10.1016/j.jneuroim.2015.07.010

Cited by 18 publications

(8 citation statements)

References 21 publications

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“…However, there are no available reports which relate chemokine and its co-receptor SNPs to JE. Till date, genetic studies associating host genotype and JE are limited only to the analysis of TNFα and TLR3 polymorphisms 28 , 29 . rs1024611G and rs2280788G are associated with communicable diseases like pulmonary tuberculosis 30 , 31 and Hepatitis C 32 , 33 .…”

Section: Discussionmentioning

confidence: 99%

Significance of CCL2, CCL5 and CCR2 polymorphisms for adverse prognosis of Japanese encephalitis from an endemic population of India

Chowdhury

Khan

2017

Sci Rep

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Japanese encephalitis (JE) is a major contributor for viral encephalitis in Asia. Vaccination programme has limited success for largely populated JE endemic countries like India and disease exposure is unavoidable. Involvement of chemokines and its co-receptors for adverse prognosis of JE have been documented both in vitro and in vivo. Identification of the genetic predisposing factor for JE infection in humans is crucial but not yet established. Therefore, we investigated the association of single nucleotide polymorphisms (SNPs) in chemokines (CCL2 and CCL5) and its co-receptors (CCR2 and CCR5) with their protein level for JE. The study enrolled 87 symptomatic JE cases (mild: severe = 24:63) and 94 asymptomatic controls. Our study demonstrated that CCL2 (rs1024611G), CCL5 (rs2280788G) and CCR2 (rs1799864A) significantly associated with JE (Odds ratio = 1.63, 2.95 and 2.62, respectively and P = 0.045, P = 0.05 and P = 0.0006, respectively). The study revealed that rs1024611G allele was associated with elevated level of CCL2. CCL5 elevation associated with JE mortality having a Cox proportional hazard of 1.004 (P = 0.033). In conclusion, SNPs of chemokine viz. CCL2 (rs1024611G) and its receptor CCR2 (rs1799864A) significantly associated with JE which may serve as possible genetic predisposing factor and CCL5 protein level may act as marker for disease survival.

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Section: Discussionmentioning

confidence: 99%

Significance of CCL2, CCL5 and CCR2 polymorphisms for adverse prognosis of Japanese encephalitis from an endemic population of India

Chowdhury

Khan

2017

Sci Rep

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“…Recently, polymorphisms in the genes encoding PRRs are reportedly associated with influenza A virus H5N1, respiratory syncytial virus, B‐type encephalitis virus, and herpes simplex virus, as well as opportunistic bacterial infection in human immunodeficiency virus‐infected individuals …”

Section: Introductionmentioning

confidence: 99%

Association of gene polymorphisms of pattern‐recognition receptor signaling pathway with the risk and severity of hand, foot, and mouth disease caused by enterovirus 71 in Chinese Han population

Jia

et al. 2018

Journal of Medical Virology

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Hand, foot, and mouth disease (HFMD) caused by enterovirus 71 (EV71) presents with a wide variety of clinical manifestations. Host immune response is a factor that influences disease susceptibility and severity. We investigated the potential association of gene polymorphisms in the pattern recognition receptor (PRR) pathway with the risk and severity of EV71 infection. A total of 180 EV71 HFMD cases (108 severe case; 72 mild cases) were enrolled. A group of 201 sex- and age-matched children was included as a control. All subjects were genotyped for the most common single-nucleotide polymorphisms (SNPs) in the PRR and the PRR signaling pathway using the SNPscan multiple SNP typing method. Binary logistic regression analysis revealed statistically significant differences in polymorphism of RIG-1 between patients and controls (rs3739674 G vs C: OR = 1.502, 95%CI: 1.120-2.014; rs9695310 G vs C: OR = 1.782, 95%CI: 1.312-2.419). Polymorphisms of RIG-1 rs3739674 (G vs C: OR = 2.047, 95%CI: 1.307-3.205) and TLR3 rs5743305 (A vs T: OR = 0.346, 95%CI: 0.212-0.566) were found to be associated with disease severity. The results indicated that RIG-1 (rs3739674 and rs9695310) polymorphisms are associated with an increased risk of EV71-induced HFMD in Chinese children, whereas RIG-1 rs3739674 and TLR3 rs5743305 polymorphisms are associated with disease severity. These findings support an important role of innate immune mechanism in EV71 infection.

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“…The L412F SNP was not associated with HCMV infection in renal transplant recipients, although it was linked with the incidence of acute rejection and graft function [21]. This polymorphism was also over-represented in other diseases, including liver recipients infected with human hepatitis C virus [46], infants with bronchiolitis [47], and individuals with asthma [40] or Japanese encephalitis [48]. The L412F SNP was also linked with resistance against HIV infection in the Italian population [49].…”

Section: Discussionmentioning

confidence: 99%

Association of TLR3 L412F Polymorphism with Cytomegalovirus Infection in Children

et al. 2017

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Intracellular Toll-like receptor 3 (TLR3) recognizes viral double-stranded RNA (dsRNA) and activates antiviral immune responses through the production of type I interferons (IFNs) and inflammatory cytokines. This receptor binds to dsRNA molecules produced during human cytomegalovirus (HCMV) replication. TLR7 senses viral single-stranded RNA (ssRNA) in endosomes, and it can interact with endogenous RNAs. We determined the genotype distribution of single-nucleotide polymorphisms (SNPs) within the TLR3 and TLR7 genes in children with HCMV infection and the relationship between TLR polymorphisms and viral infection. We genotyped 59 children with symptomatic HCMV infection and 78 healthy individuals for SNPs in the TLR3 (rs3775290, c.1377C>T, F459F; rs3775291, c.1234C>T, L412F; rs3775296, c.-7C>A) and TLR7 (rs179008, c.32A>T, Q11L; rs5741880, c.3+1716G>T) genes. SNP genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and capillary electrophoresis. The HCMV DNA load was quantified by real-time PCR. We found an increased frequency of the heterozygous genotype TLR3 L412F in children with HCMV infection compared with uninfected cases. In individuals with a mutation present in at least one allele of the L412F SNP, an increased risk of HCMV disease was found, and this result remained highly significant after Bonferroni’s correction for multiple testing (Pc < 0.001). The heterozygous genotype of this SNP was associated with the increased risk of HCMV disease in an adjusted model that included the HCMV DNA copy number in whole blood and urine (P < 0.001 and P = 0.008, respectively). Moreover, those with a heterozygous genotype of rs3775296 showed an increased relative risk of HCMV infection (P = 0.042), but this association did not reach statistical significance after correction for multiple testing. In contrast, the rs3775290 SNP of TLR3 and TLR7 SNPs were not related to viral infection. A moderate linkage disequilibrium (LD) was observed between the SNPs rs3775291 and rs3775296 (r2 = 0.514). We suggest that the L412F polymorphism in the TLR3 gene could be a genetic risk factor for the development of HCMV disease.

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Toll-like receptor-3 gene polymorphism in patients with Japanese encephalitis

Cited by 18 publications

References 21 publications

Significance of CCL2, CCL5 and CCR2 polymorphisms for adverse prognosis of Japanese encephalitis from an endemic population of India

Significance of CCL2, CCL5 and CCR2 polymorphisms for adverse prognosis of Japanese encephalitis from an endemic population of India

Association of gene polymorphisms of pattern‐recognition receptor signaling pathway with the risk and severity of hand, foot, and mouth disease caused by enterovirus 71 in Chinese Han population

Association of TLR3 L412F Polymorphism with Cytomegalovirus Infection in Children

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