TY - JOUR

T1 - A matrix metalloproteinase 9 (MMP9) gene single nucleotide polymorphism is associated with predisposition to tick-borne encephalitis virus-induced severe central nervous system disease

AU - Barkhash, Andrey V.

AU - Yurchenko, Andrey A.

AU - Yudin, Nikolay S.

AU - Ignatieva, Elena V.

AU - Kozlova, Irina V.

AU - Borishchuk, Inessa A.

AU - Pozdnyakova, Larisa L.

AU - Voevoda, Mikhail I.

AU - Romaschenko, Aida G.

N1 - Publisher Copyright: © 2018 Elsevier GmbH

PY - 2018/5/1

Y1 - 2018/5/1

N2 - 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.

AB - 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.

KW - Genetic predisposition

KW - Matrix metalloproteinase 9 (MMP9) gene

KW - Single nucleotide polymorphism (SNP)

KW - Tick-borne encephalitis (TBE)

KW - Whole-exome sequencing

KW - MOLECULAR-BIOLOGY

KW - VARIANTS

KW - SUSCEPTIBILITY

KW - RUSSIAN POPULATION

KW - REGION

KW - MATRIX METALLOPROTEINASES

KW - BIOCHEMISTRY

KW - GELATINASE-B

KW - SEQUENCING DATA

KW - TLR3

UR - http://www.scopus.com/inward/record.url?scp=85039728524&partnerID=8YFLogxK

U2 - 10.1016/j.ttbdis.2018.02.010

DO - 10.1016/j.ttbdis.2018.02.010

M3 - Article

AN - SCOPUS:85039728524

VL - 9

SP - 763

EP - 767

JO - Ticks and Tick-borne Diseases

JF - Ticks and Tick-borne Diseases

SN - 1877-959X

IS - 4

ER -