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Association of toll-like receptors polymorphism and intrauterine transmission of cytomegalovirus.

ABSTRACT: Congenital Cytomegalovirus (CMV) is a very common intrauterine infection which can cause severe developmental disabilities. Transmission of the virus to the fetus occurs in only 40% of primarily infected women. The probability of intrauterine transmission is higher when infection occurs during the second trimester of pregnancy than in the first trimester. The Toll-like receptors (TLRs) protein family plays a key role in both innate immune response to CMV infections and in normal pregnancy. Specific single nucleotide polymorphisms (SNPs) in TLRs can affect CMV infections and maternal-fetal interface expression. Therefore, TLR SNPs could be involved in intrauterine transmission determination.To establish a correlation between TLR2 (rs4696480, rs3804100, rs1898830), TLR3 (rs3775291) and TLR7(rs179008) SNPs with CMV intrauterine transmission during the first and second trimester.SNPs of 83 pregnant women with primary CMV were analyzed by Real-Time PCR and PCR-RFLP assay and compared to intrauterine transmission state.Women bearing the GG genotype in the rs1898830 TLR2 SNP who were infected with CMV during the second trimester did not transmit the virus to the fetus. Likewise, in the co-dominant or recessive models of this SNP, a significant association was found between the genotypes and CMV intrauterine transmission. In all cohort women or in women infected during the first trimester, no such associations were found between the tested SNPs and intrauterine transmission of the virus.Women bearing the GG genotype in the rs1898830 SNP, who are infected with CMV during the second trimester of pregnancy, have a low likelihood of transmitting the virus to the fetus.

SUBMITTER: Eldar-Yedidia Y

PROVIDER: S-EPMC5739442 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Association of toll-like receptors polymorphism and intrauterine transmission of cytomegalovirus.

Eldar-Yedidia Yifat Y Hillel Miriam M Cohen Amitay A Bar-Meir Maskit M Freier-Dror Yossi Y Schlesinger Yechiel Y

PloS one 20171221 12

<h4>Background</h4>Congenital Cytomegalovirus (CMV) is a very common intrauterine infection which can cause severe developmental disabilities. Transmission of the virus to the fetus occurs in only 40% of primarily infected women. The probability of intrauterine transmission is higher when infection occurs during the second trimester of pregnancy than in the first trimester. The Toll-like receptors (TLRs) protein family plays a key role in both innate immune response to CMV infections and in norm ...[more]

PMID: 29267374

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Project description: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.

Dataset Information

Association of toll-like receptors polymorphism and intrauterine transmission of cytomegalovirus.

Publications

Association of toll-like receptors polymorphism and intrauterine transmission of cytomegalovirus.

Similar Datasets

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