A matrix metalloproteinase 9 (MMP9) gene single nucleotide polymorphism is associated with predisposition to tick-borne encephalitis virus-induced severe central nervous system disease.

The progression of infectious diseases depends on causative agents, the environment and the host's genetic susceptibility. To date, human genetic susceptibility to tick-borne encephalitis (TBE) virus-induced disease has not been sufficiently studied. We have combined whole-exome sequencing with a candidate gene approach to identify genes that are involved in the development of predisposition to TBE in a Russian population. Initially, six exomes from TBE patients with severe central nervous system (CNS) disease and seven exomes from control individuals were sequenced. Despite the small sample size, two nonsynonymous single nucleotide polymorphisms (SNPs) were significantly associated with TBE virus-induced severe CNS disease. One of these SNPs is rs6558394 (G/A, Pro422Leu) in the scribbled planar cell polarity protein (SCRIB) gene and the other SNP is rs17576 (A/G, Gln279Arg) in the matrix metalloproteinase 9 (MMP9) gene. Subsequently, these SNPs were genotyped in DNA samples of 150 non-immunized TBE patients with different clinical forms of the disease from two cities and 228 control randomly selected samples from the same populations. There were no statistically significant differences in genotype and allele frequencies between the case and control groups for rs6558394. However, the frequency of the rs17576 G allele was significantly higher in TBE patients with severe CNS diseases such as meningo-encephalitis (43.5%) when compared with TBE patients with milder meningitis (26.3%; P = 0.01), as well as with the population control group (32.5%; P = 0.042). The results suggest that the MMP9 gene may affect genetic predisposition to TBE in a Russian population.

Barkhash AV ，Yurchenko AA ，Yudin NS ，Ignatieva EV ，Kozlova IV ，Borishchuk IA ，Pozdnyakova LL ，Voevoda MI ，Romaschenko AG ... -  《-》

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

Tick-borne encephalitis (TBE) is a central nervous system (CNS) disease caused by the neurotropic, positive-sense RNA virus, tick-borne encephalitis virus (TBEV). A possible association between predisposition to TBE in a Russian population and two polymorphisms, a 32bp deletion in the coding region of the chemokine receptor CCR5 gene and the rs3775291 single nucleotide polymorphism (SNP) (G/A, Leu412Phe) in exon 4 of the toll-like receptor TLR3 gene, was investigated. The genotypic and allelic frequencies of these polymorphisms were analyzed in 137 non-immunized TBE patients with different clinical manifestations, including fever (35), meningitis (62), and severe CNS disease (40), as well as in a control population (269 randomly selected Novosibirsk citizens). The frequencies of the TLR3 G allele and G/G homozygotes were significantly higher among the patients with TBE compared with the control group (P=0.029 and 0.037, respectively), especially among patients with severe disease (P=0.018 and 0.017, respectively). These results indicate that the G allele (within the G/G homozygous genotype) of the TLR3 rs3775291 SNP is associated with predisposition to TBE in the Russian population.

Barkhash AV ，Voevoda MI ，Romaschenko AG 《-》

Association of IL28B and IL10 gene polymorphism with predisposition to tick-borne encephalitis in a Russian population.

Genetic predisposition to tick-borne encephalitis (TBE) is rather poorly studied in human populations. Human genes encoding crucial components of antiviral immune response are most likely involved in protective mechanisms against TBE virus. Previously, several single nucleotide polymorphisms (SNPs) located in interleukin 28B (IL28B) and interleukin 10 (IL10) genes were associated with predisposition to chronic hepatitis C (caused by a structurally similar virus from the same Flaviviridae family) in a number of human populations. The aim of the present study was to estimate a possible association of the IL28B gene rs8103142 and rs12980275 SNPs and IL10 gene rs1800872, rs3021094, and rs3024498 SNPs with predisposition to TBE in a Russian population. Genotypic and allelic frequencies for these SNPs were analyzed in 132 non-immunized TBE patients (34 with fever, 60 with meningitis, and 38 with severe central nervous system disease) and compared with the population control (221 Novosibirsk citizens). The results obtained suggest that both studied IL28B gene SNPs, as well as the IL10 gene rs1800872 SNP are associated with predisposition to TBE in Russian population.

Barkhash AV ，Babenko VN ，Voevoda MI ，Romaschenko AG ... -  《-》

Exome-wide search and functional annotation of genes associated in patients with severe tick-borne encephalitis in a Russian population.

Ignatieva EV ，Yurchenko AA ，Voevoda MI ，Yudin NS ... -  《BMC Medical Genomics》

Single nucleotide polymorphism in the promoter region of the CD209 gene is associated with human predisposition to severe forms of tick-borne encephalitis.

Tick-borne encephalitis virus (TBEV) is a neurotropic, positive-sense RNA virus of the genus Flavivirus (family Flaviviridae) which can cause a variety of clinical manifestations in humans. Previously the severity and outcome of dengue fever and hepatitis C (diseases caused by viruses from the family Flaviviridae) were associated with the rs4804803 single nucleotide polymorphism (SNP) located in the promoter region of the human CD209 gene. This gene encodes dendritic cell-specific ICAM3-grabbing nonintegrin (DC-SIGN), a C-type lectin pathogen-recognition receptor expressed on the surface of dendritic cells and some types of macrophages. In the current study, a possible association between two SNPs in the promoter region of the CD209 gene (rs4804803 and rs2287886) and predisposition to severe forms of TBEV-induced disease was investigated. The genotypic, allelic and haplotypic frequencies of these SNPs were analyzed in 136 non-immunized Russian patients with different clinical manifestations of tick-borne encephalitis (TBE) and in a control group. An increase in the frequency of the rs2287886 SNP AA homozygotes and the A allele was detected among patients with severe central nervous system disease compared with the group of patients with meningitis (P=0.003 and 0.019), or a combined group of patients with mild forms (fever and meningitis) (P=0.003 and 0.026), or the control group (P=0.007 and 0.035). Thus, our results suggest that the CD209 gene promoter region rs2287886 SNP is associated with predisposition to severe forms of TBE in the Russian population.

Barkhash AV ，Perelygin AA ，Babenko VN ，Brinton MA ，Voevoda MI ... -  《-》