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Toll-like receptors genes polymorphisms and the occurrence of HCMV infection among pregnant women.

ABSTRACT: Human cytomegalovirus (HCMV) is the most common cause of intrauterine infections worldwide. The toll-like receptors (TLRs) have been reported as important factors in immune response against HCMV. Particularly, TLR2, TLR4 and TLR9 have been shown to be involved in antiviral immunity. Evaluation of the role of single nucleotide polymorphisms (SNPs), located within TLR2, TLR4 and TLR9 genes, in the development of human cytomegalovirus (HCMV) infection in pregnant women and their fetuses and neonates, was performed.The study was performed for 131 pregnant women, including 66 patients infected with HCMV during pregnancy, and 65 age-matched control pregnant individuals. The patients were selected to the study, based on serological status of anti-HCMV IgG and IgM antibodies and on the presence of viral DNA in their body fluids. Genotypes in TLR2 2258 A?>?G, TLR4 896 G?>?A and 1196 C?>?T and TLR9 2848 G?>?A SNPs were determined by self-designed nested PCR-RFLP assays. Randomly selected PCR products, representative for distinct genotypes in TLR SNPs, were confirmed by sequencing. A relationship between the genotypes, alleles, haplotypes and multiple variants in the studied polymorphisms, and the occurrence of HCMV infection in pregnant women and their offsprings, was determined, using a logistic regression model.Genotypes in all the analyzed polymorphisms preserved the Hardy-Weinberg equilibrium in pregnant women, both infected and uninfected with HCMV (P?>?0.050). GG homozygotic and GA heterozygotic status in TLR9 2848 G?>?A SNP decreased significantly the occurrence of HCMV infection (OR 0.44 95% CI 0.21-0.94 in the dominant model, P???0.050). The G allele in TLR9 SNP was significantly more frequent among the uninfected pregnant women than among the infected ones (?2?=?4.14, P???0.050). Considering other polymorphisms, similar frequencies of distinct genotypes, haplotypes and multiple-SNP variants were observed between the studied groups of patients.TLR9 2848 G?>?A SNP may be associated with HCMV infection in pregnant women.

SUBMITTER: Wujcicka W

PROVIDER: S-EPMC5364709 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Toll-like receptors genes polymorphisms and the occurrence of HCMV infection among pregnant women.

Wujcicka Wioletta W Paradowska Edyta E Studzińska Mirosława M Wilczyński Jan J Nowakowska Dorota D

Virology journal 20170324 1

<h4>Background</h4>Human cytomegalovirus (HCMV) is the most common cause of intrauterine infections worldwide. The toll-like receptors (TLRs) have been reported as important factors in immune response against HCMV. Particularly, TLR2, TLR4 and TLR9 have been shown to be involved in antiviral immunity. Evaluation of the role of single nucleotide polymorphisms (SNPs), located within TLR2, TLR4 and TLR9 genes, in the development of human cytomegalovirus (HCMV) infection in pregnant women and their ...[more]

PMID: 28340580

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Project description:This retrospective study aims to identify the single nucleotide polymorphisms (SNPs) of 5,10-methylenetetrahydrofolate reductase (MTHFR) (C677T, A1298C), methionine synthase reductase (MTRR) (A66G) and ethnic distribution characteristics in pregnant women, and to explore the risk correlation with folate metabolism. The demographic data of 8735 pregnant women aged 15 to 47 years were retrospectively analyzed, and peripheral blood samples were collected and tested. Reverse transcription-quantitative polymerase chain reaction was applied to determine the genotype and allele frequency of MTHFR C677T, A1298C and MTRR A66G in blood samples. Sperman correlation analysis, univariate and multivariate logistic regression analysis were used to verify the correlation between SNPs of MTHFR (C677T, A1298C), MTRR (A66G), different ethnic groups and the susceptibility and risk levels of folate metabolism. The relative risk of the SNPs was further determined by calculating the odds ratio (OR) at a 95% confidence interval (CI). The average age of 8735 pregnant women was 28.87 ± 4.20 years old. The evaluation of risk levels for folate metabolism was relative high, including 2296 cases with low risk, 3971 cases with medium risk, and 752 cases with high risk. Among the MTHFR C677T locus, the CC genotype had the highest frequency, MTHFR A1298C locus had the highest frequency of the AA genotype, and MTRR A66G locus had the highest frequency of the AA genotype. The frequency distribution of SNPs in different ethnic groups revealed that the frequency of CT genotype among the MTHFR C677T locus, AA genotype among the MTHFR A1298C locus and the MTRR A66G locus was the highest in Han, Buyi, Miao and Dong ethnic groups. The results of logistic regression analysis showed that the Han, Buyi, Miao and other ethnic groups (including Yi, Bai, Zhuang, Chuanqing) had the possibility of increasing the risk levels of folate metabolism. The CC genotype of MTHFR C677T (adjusted OR = 2.46, 95% CI: 2.14-2.84, P < .001) and the AG genotype of MTRR A66G (adjusted OR = 1.89, 95% CI: 1.61-2.22, P < .001) were significantly related to the risk levels of folate metabolism, which is an independent risk factor for the susceptibility of folate metabolism.

Dataset Information

Toll-like receptors genes polymorphisms and the occurrence of HCMV infection among pregnant women.

Publications

Toll-like receptors genes polymorphisms and the occurrence of HCMV infection among pregnant women.

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