Fatima Tanzeem, Syed Asad, Elgorban Abdallah M, Abid Islem, Wong Ling Shing, Khan Mohd Sajid, Khatoon Jahanarah, Sharma Puneet Kumar
Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
Department of Microbiology, King George's Medical University, Lucknow, Uttar Pradesh, India.
Reprod Sci. 2025 Jun 20. doi: 10.1007/s43032-025-01912-9.
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.
人巨细胞病毒（HCMV）是全球40%-100%孕妇发生宫内感染（影响人类健康）的主要原因，在高收入国家感染率较低，在低收入和中等收入地区感染率较高，且可垂直传播给胎儿。TLR4基因的突变因增加对多种病毒、细菌和寄生虫疾病的易感性而为人所知。本研究旨在调查TLR4 Asp299Gly和Thr399Ile基因多态性与孕妇感染HCMV易感性之间的相关性。本研究共纳入400名孕妇，其中150名在孕期感染HCMV，250名年龄匹配的未感染病毒的对照个体，年龄在18至40岁之间。提取DNA，并使用基于PCR的基因分型检测方法进行PCR，以筛查HCMV感染和TLR4等位基因特异性多态性。这是通过采用PCR的基因分型程序实现的。计算TLR4 SNP中基因型和等位基因的患病率；通过描述性统计分析HCMV感染和未感染孕妇的情况。结果表明，TLR4 Asp299Gly和Thr399Ile多态性的杂合基因型女性感染HCMV的易感性增加（分别为p = 0.037和p = 0.024）。我们的分析显示，携带Gly和Ile等位基因的个体对HCMV感染的易感性更高（分别为p = 0.013和p = 0.001）。与对照组相比，IIe/Gly单倍型与患病概率显著相关（p = 0.006）。TLR4 mRNA表达增加与HCMV阳性之间也存在相关性（p = 0.04）。因此，TLR4基因（Asp299Gly和Thr399Ile）的多态性似乎与孕妇HCMV感染的发生有关。
