BackgroundSome single nucleotide polymorphisms (SNP), located in Toll-like receptor (TLR) genes, were reported to be associated with human cytomegalovirus (HCMV) infections. The study was aimed to assess the correlation of SNPs at TLR4 and TLR9 genes with the occurrence of congenital cytomegaly, based on available samples.MethodsReported case-control study included both HCMV infected and non-infected fetuses and newborns. The specimens were classified to the molecular analyses, based on serological features of the recent infection and HCMV DNAemia in body fluids. TLR SNPs were studied, using multiplex nested PCR-RFLP assay, and determined genotypes were confirmed by sequencing. Hardy-Weinberg equilibrium was assessed for the identified genotypes. The linkage disequilibrium was also estimated for TLR4 SNPs. A relationship between the status of TLR genotypes and congenital cytomegaly development was estimated, using a logistic regression model.ResultsHardy Weinberg equilibrium was observed for almost all SNPs, both infected and non-infected patients, with exception of TLR4 896 A>G polymorphism in the control group (P≤0.050). TLR4 896 A>G and 1196 C>T SNPs were found in linkage disequilibrium in both study groups (P≤0.050). The CC genotype at TLR4 1196 SNP and the GA variant at TLR9 2848 G>A SNP were significantly associated with HCMV infection (P≤0.050). The risk of congenital cytomegaly was higher in heterozygotes at TLR9 SNP than in the carriers of other genotypic variants at the reported locus (OR 4.81; P≤0.050). The GC haplotype at TLR4 SNPs and GCA variants at TLR4 and TLR9 SNPs were significantly associated with HCMV infection (P≤0.0001). The ACA variants were more frequent among fetuses and neonates with symptomatic, rather than asymptomatic cytomegaly (P≤0.0001).Conclusions TLR4 and TLR9 polymorphisms may contribute to the development of congenital infection with HCMV in fetuses and neonates. The TLR9 2848 GA heterozygotic status possibly predisposes to HCMV infection, increasing the risk of congenital cytomegaly development.
The aim of this study was to review the role of selected trace elements in pregnancy and fetal development. Citations related to the role of iron (Fe), zinc (Zn), manganese (Mn), copper (Cu) and selenium (Se) during pregnancy were searched in PubMed, Medline, Web of Science, using keywords and MeSH terms. Inadequate supply of trace elements can cause abnormalities of fetal development and predispose a child to disorders later on in life. Trace elements are the key elements of complex enzymes responsible for the modulation of the antioxidant defense system of the organism. It has been suggested that there is a correlation between reduced levels of trace elements essential for antioxidant function in the body of pregnant women, and an increased risk of developing preeclampsia. Trace elements are components of numerous regulatory enzymes and hormones essential to the division and differentiation of fetal cells and their further development. Mineral deficiencies in pregnant women can cause birth defects of the central nervous system, and growth disorders. Future research should be directed to explain the interaction between trace elements, and establish the optimum levels of macro and micronutrients supplementation, as well as determine the reference values for trace elements in the maternal serum, umbilical cord blood and amniotic fluid.
Toll-like receptor 9 (TLR9) recognizes non-methylated viral CpG-containing DNA and serves as a pattern recognition receptor that signals the presence of human cytomegalovirus (HCMV). Here, we present the genotype distribution of single-nucleotide polymorphisms (SNPs) of the TLR9 gene in infants and the relationship between TLR9 polymorphisms and HCMV infection. Four polymorphisms (-1237T/C, rs5743836; -1486T/C, rs187084; 1174G/A, rs352139; and 2848C/T, rs352140) in the TLR9 gene were genotyped in 72 infants with symptomatic HCMV infection and 70 healthy individuals. SNP genotyping was performed by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Digested fragments were separated and identified by capillary electrophoresis. The HCMV DNA copy number was measured by a quantitative real-time PCR assay. We found an increased frequency of heterozygous genotypes TLR9 -1486T/C and 2848C/T in infants with HCMV infection compared with uninfected cases. Heterozygous variants of these two SNPs increased the risk of HCMV disease in children (P = 0.044 and P = 0.029, respectively). In infants with a mutation present in at least one allele of -1486T/C and 2848C/T SNPs, a trend towards increased risk of cytomegaly was confirmed after Bonferroni’s correction for multiple testing (Pc = 0.063). The rs352139 GG genotype showed a significantly reduced relative risk for HCMV infection (Pc = 0.006). In contrast, the -1237T/C SNP was not related to viral infection. We found no evidence for linkage disequilibrium with the four examined TLR9 SNPs. The findings suggest that the TLR9 -1486T/C and 2848C/T polymorphisms could be a genetic risk factor for the development of HCMV disease.
The purpose of this investigation was to perform an evaluation of the prevalence and socioeconomic risk factors for human cytomegalovirus (HCMV) infections in a cohort of Polish pregnant women between 2010 and 2011. HCMV-specific IgG and IgM antibody levels were assayed with enzyme-linked immunosorbent assay (ELISA) tests in serum samples collected from 1,250 pregnant women attending outpatient obstetric clinics and hospitalized at two hospitals in Lodz. The seroprevalence of anti-HCMV IgG and IgM antibodies was 62.4 and 2.2 %, respectively, and differed significantly between age-stratified groups (p ≤ 0.05). The highest IgG prevalence was observed in women above 36 years of age (76.2 %) and IgM in adolescent women aged 16–20 years (6.0 %). Of the various socioeconomic factors, age above 36 years, basic and professional education, and offspring were significantly associated with HCMV IgG prevalence rates (PRs; 1.89, 1.80, and 1.56, respectively). Financial status, occupational risk related to contact with children, and transfusions were not related to the prevalence of IgG antibodies. The IgM prevalence was not associated with any of the analyzed risk factors. A slightly higher prevalence was observed in women who were transfused in the past, but the relationship was not significant. The current data have revealed a decrease in HCMV IgG seroprevalence in our region during recent years (62.4 vs. 76.7 %). Basic and professional education, as well as bringing up offspring, were determined as significant risk factors for HCMV infections in Polish pregnant women [risk ratio (RR) 1.20 and 1.17, respectively], suggesting that the primary and secondary prophylaxis of cytomegaly is necessary during pregnancy, even if screening is not mandatory.
Human cytomegalovirus (HCMV) is the most common congenital infection. HCMV strains display genetic variability in different regions. Distribution of HCMV genotypes in the population of congenitally infected newborns from Central Poland and viral load in newborns' blood is described and discussed. HCMV isolates were analysed by sequencing at three sites on the genome: the UL144 tumour necrosis factor-alpha (TNFα)-like receptor gene, the US28 beta-chemokine receptor gene and the UL55 envelope glycoprotein B (gB) gene. The newborns' blood was examined for HCMV DNA with a nested (UL144, UL55) or heminested (US28) polymerase chain reaction, and the genotypes were determined by sequence analysis. HCMV DNA was detectable in 25 out of 55 examined newborns born by HCMV-infected mothers (45.5%). The blood viral load in mother-infant pairs was determined. Most of the newborns had identical virus genotype, gB2 (96%), UL144 B1 (88%) and US28 A2 (84%). These genotypes were detected in all newborns with asymptomatic congenital infection. The occurrence of UL144 B1 or US28 A2 genotypes in the babies examined was significant in comparison to other genotypes (p=0.0002 and p=0.040 respectively). There was no association between specific gB subtypes in all patients groups (p=0.463). There was no correlation between HCMV genotypes and the outcome.
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