Association of single nucleotide polymorphism rs3775291 in the coding region of the TLR3 gene with predisposition to tick-borne encephalitis in a Russian population

Barkhash, Andrey V.; Воевода, М. И.; Romaschenko, A. G.

doi:10.1016/j.antiviral.2013.05.008

Cited by 53 publications

(33 citation statements)

References 19 publications

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“…In the recently published study, no association between CCR5 polymorphism and predisposition to TBE was found in the Russian population [26]. Although the findings on TLR3 in the Russian report were in agreement with our data, major differences in design make comparison of the results difficult.…”

Section: Discussionsupporting

confidence: 87%

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Polymorphisms in Chemokine Receptor 5 and Toll-Like Receptor 3 Genes Are Risk Factors for Clinical Tick-Borne Encephalitis in the Lithuanian Population

et al. 2014

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BackgroundTick-borne encephalitis virus (TBEV) infections can be asymptomatic or cause moderate to severe injuries of the nervous system. We previously reported that a nonfunctional chemokine receptor 5 (CCR5) and a functional Toll-like receptor 3 (TLR3) predispose adults to clinical tick-borne encephalitis (TBE). This study expands our previous findings and further examines polymorphisms in CCR5 and TLR3 genes in different age and disease severity groups.Methods117 children and 129 adults, stratified into mild, moderate and severe forms of TBE, and 103 adults with severe TBE were analyzed. 135 healthy individuals and 79 patients with aseptic meningoencephalitis served as controls. CCR5 delta 32 and rs3775291 TLR3 genotypes were established by pyrosequencing, and their frequencies were analyzed using recessive genetic, genotype and allelic models.FindingsThe prevalence of CCR5Δ32 homozygotes was higher in children (2.5%), in adults with severe TBE (1.9%), and in the combined cohort of TBE patients (2.3%) than in controls (0%) (p<0.05). The nonfunctional homozygous TLR3 genotype was less prevalent among the combined TBE cohort (11.5%) than among controls (19.9%) (p = 0.025), but did not differ between children TBE and controls. The genotype and allele prevalence of CCR5 and TLR3 did not differ in children nor adult TBE cohorts stratified by disease severity. However, in the severe adult TBE cohort, homozygous functional TLR3 genotype and wt allele were less prevalent compared to the adult cohort with the whole disease severity spectrum (44.4% vs 59.8% p = 0.022 and 65.2% vs 76.4% p = 0.009; respectively).ConclusionsIndependently of age, nonfunctional CCR5Δ32 mutation is a significant risk factor for development of clinical TBE, but not for disease severity. The polymorphism of TLR3 gene predisposes to clinical TBE in adults only and may be associated with disease severity. Further studies are needed to clarify the role of these polymorphisms in susceptibility to TBEV infection.

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Section: Discussionsupporting

confidence: 87%

“…To the best of our knowledge, only one other research group has studied the role of human genetics in TBE [24]–[26]. In the recently published study, no association between CCR5 polymorphism and predisposition to TBE was found in the Russian population [26].…”

Section: Discussionmentioning

confidence: 94%

Polymorphisms in Chemokine Receptor 5 and Toll-Like Receptor 3 Genes Are Risk Factors for Clinical Tick-Borne Encephalitis in the Lithuanian Population

et al. 2014

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“…Although this study evaluated a small number of patients, these data suggest that the CCR5Δ32 mutation may be a risk factor for developing severe disease after TBEV infection. In a follow up study by Barkhash et al (2013) using a larger cohort, the authors found no significant association between CCR5Δ32 mutation and predisposition to TBE.…”

Section: The Role Of Chemokine Receptors In the Pathogenesis Of Arbovmentioning

confidence: 89%

Chemokine receptors as important regulators of pathogenesis during arboviral encephalitis

Michlmayr

Lim

2014

Front. Cell. Neurosci.

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The central nervous system (CNS) is a highly complex network comprising long-lived neurons and glial cells. Accordingly, numerous mechanisms have evolved to tightly regulate the initiation of inflammatory responses within the brain. Under neuroinflammatory conditions, as in the case of viral encephalitides, the infiltration of leukocytes is often required for efficient viral clearance and recovery. The orchestration of leukocyte migration into the inflamed CNS is largely coordinated by a large family of chemotactic cytokines and their receptors. In this review, we will summarize our current understanding of how chemokines promote protection or pathogenesis during arbovirus induced encephalitis, focusing on neurotropic flaviviruses and alphaviruses. Furthermore, we will highlight the latest developments in chemokine and chemokine receptor based drugs that could have potential as therapeutics and have been shown to play a pivotal role in shaping the outcome of disease.

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“…Earlier study suggested that TLR4 induced cytokines such as IL-6, IL-12 and IFN-γ regulate the immune response against dengue virus (Azeredo et al, 2010). Studies have shown that the TLR4 gene SNPs affect its function and found to be associated with several viral diseases such as HIV-1 and HSV-2 infections, viral encephalitis, and mortality in Crimean Congo hemorrhagic fever (CCHF) (Barkhash et al, 2013;Kindberg et al, 2011;Sironi et al, 2012;Svensson et al, 2012).…”

Section: Discussionmentioning

confidence: 97%

Analysis of TLR4 (Asp299Gly and Thr399Ile) gene polymorphisms and mRNA level in patients with dengue infection: A case-control study

Sharma

Singh

Kakkar

et al. 2016

Infection, Genetics and Evolution

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Association of single nucleotide polymorphism rs3775291 in the coding region of the TLR3 gene with predisposition to tick-borne encephalitis in a Russian population

Cited by 53 publications

References 19 publications

Polymorphisms in Chemokine Receptor 5 and Toll-Like Receptor 3 Genes Are Risk Factors for Clinical Tick-Borne Encephalitis in the Lithuanian Population

Polymorphisms in Chemokine Receptor 5 and Toll-Like Receptor 3 Genes Are Risk Factors for Clinical Tick-Borne Encephalitis in the Lithuanian Population

Chemokine receptors as important regulators of pathogenesis during arboviral encephalitis

Analysis of TLR4 (Asp299Gly and Thr399Ile) gene polymorphisms and mRNA level in patients with dengue infection: A case-control study

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