Role of TLR4 Asp299Gly and Thr399Ile Gene Polymorphisms as a Risk Factor in Human Cytomegalovirus Positive Pregnant Women.

Abstract

Human cytomegalovirus (HCMV) is the primary cause of intra-uterine infections (human health) affecting 40-100% of pregnant women globally, with lower rates observed in high-income countries and higher rates in low- and middle-income regions, and it is vertically transmitted to fetus. Mutation in the TLR4 gene is known for enhanced predisposition to several viral, bacterial, and parasitic diseases. This study aimed to investigate the correlation between TLR4 Asp299Gly and Thr399Ile gene polymorphisms and vulnerability to HCMV infection in pregnant women. A total of 400 pregnant women, 150 patients infected with HCMV during pregnancy and 250 age-matched control individuals uninfected with virus, age between 18 and 40 years were included in this study. DNA was extracted and PCR was carried out for screening HCMV infection and TLR4 allele-specific polymorphisms using PCR-based genotyping assay. This was achieved by a genotyping procedure that employs PCR. Prevalence rates of genotypes and alleles in TLR4 SNP were calculated; both in the HCMV infected and uninfected pregnant women by means of descriptive statistics. The results suggested that women with a heterozygous genotype for TLR4 Asp299Gly and Thr399Ile polymorphisms have an increased predisposition to HCMV infection (p = 0.037 and p = 0.024, respectively). Our analysis revealed that individuals with Gly and Ile alleles had a higher susceptibility to HCMV infection (p = 0.013 and p = 0.001, respectively). The IIe/Gly haplotype showed a significant correlation with the probability of illness compared to the control group (p = 0.006). A correlation was also seen between increased TLR4 mRNA expression and HCMV positivity (p = 0.04). Thus, polymorphisms in the TLR4 gene (Asp299Gly and Thr399Ile) seem to contribute to the occurrence of HCMV infection in pregnant women.