Wujcicka Wioletta, Paradowska Edyta, Studzińska Mirosława, Wilczyński Jan, Nowakowska Dorota
Scientific Laboratory of the Center of Medical Laboratory Diagnostics and Screening, Polish Mother's Memorial Hospital - Research Institute, 281/289 Rzgowska Street, Lodz, 93-338, Poland.
Department of Perinatology and Gynecology, Polish Mother's Memorial Hospital - Research Institute, Lodz, Poland.
Virol J. 2017 Jan 24;14(1):12. doi: 10.1186/s12985-016-0679-z.
Human cytomegalovirus (HCMV) is responsible for the most common intrauterine infections, which may be acquired congenitally from infected pregnant woman to fetus. The research was aimed to estimate the role of three single nucleotide polymorphisms (SNPs) located in TLR2 gene, and the common contribution of TLR2, and previously studied TLR4 and TLR9 SNPs, to the occurrence of congenital HCMV infection in fetuses and newborns.
The study was performed in 20 Polish fetuses and newborns, congenitally infected with HCMV, and in 31 uninfected controls, as well as with participation of pregnant women, the mothers of 16 infected and 14 uninfected offsprings. Genotypes in TLR2 SNPs were determined, using self-designed nested PCR-RFLP assays, and confirmed by sequencing. The genotypes were tested for Hardy-Weinberg (H-W) equilibrium, and for their relationship with the development of congenital cytomegaly, using a logistic regression model. The common influence of TLR2, TLR4 and TLR9 SNPs on the occurrence of congenital disease was estimated by multiple-SNP analysis.
Distribution of the genotypes and alleles in TLR2 1350 T>C and 2029 C>T SNPs was similar between the studied groups of fetuses and neonates. In case of 2258 G>A polymorphism, the GA heterozygotic status was significantly more frequent in the infected cases than among the uninfected individuals (25.0% vs. 3.2%, respectively), and increased the risk of HCMV infection (OR 10.00, 95% CI 1.07-93.44; P ≤ 0.050). Similarly, the A allele within 2258 G>A polymorphism was significantly more frequent among the infected offsprings than in the uninfected ones (12.5% vs. 1.6%; P ≤ 0.050). Complex AA variants for both TLR2 2258 and TLR9 2848 G>A polymorphisms, were estimated to be at increased risk of congenital HCMV infection (OR 11.58, 95% CI 1.19-112.59; P ≤ 0.050). Additionally, significant relationships were observed between the occurrence of complex AA or GA variants for both TLR2 and TLR9 SNPs and the increased viral loads, determined in fetal amniotic fluids and in maternal blood or urine specimens (P ≤ 0.050).
Among various TLR2, TLR4 and TLR9 polymorphisms, TLR2 2258 G>A SNP seems to be an important factor associated with increased risk of congenital HCMV infection in Polish fetuses and neonates.
人巨细胞病毒（HCMV）是最常见的宫内感染病原体，可通过感染的孕妇先天性传播给胎儿。本研究旨在评估位于TLR2基因上的三个单核苷酸多态性（SNP）的作用，以及TLR2与先前研究的TLR4和TLR9 SNP对胎儿和新生儿先天性HCMV感染发生的共同影响。
本研究纳入了20例先天性感染HCMV的波兰胎儿和新生儿以及31例未感染的对照，同时还有孕妇参与，其中16例感染后代和14例未感染后代的母亲。使用自行设计的巢式PCR-RFLP分析法确定TLR2 SNP的基因型，并通过测序进行确认。对基因型进行Hardy-Weinberg（H-W）平衡检验，并使用逻辑回归模型检验它们与先天性巨细胞病毒感染发展的关系。通过多SNP分析评估TLR2、TLR4和TLR9 SNP对先天性疾病发生的共同影响。
在研究的胎儿和新生儿组中，TLR2 1350 T>C和2029 C>T SNP的基因型和等位基因分布相似。对于2258 G>A多态性，GA杂合状态在感染病例中显著高于未感染个体（分别为25.0%和3.2%），并增加了HCMV感染的风险（OR 10.00，95% CI 1.07-93.44；P≤0.050）。同样，2258 G>A多态性中的A等位基因在感染后代中显著高于未感染后代（12.5%对1.6%；P≤0.050）。TLR2 2258和TLR9 2848 G>A多态性的复合AA变体被估计具有先天性HCMV感染风险增加（OR 11.58，95% CI 1.19-112.59；P≤0.050）。此外，在胎儿羊水以及母体血液或尿液标本中测定的病毒载量增加与TLR2和TLR9 SNP的复合AA或GA变体的发生之间观察到显著关系（P≤0.050）。
在各种TLR2、TLR4和TLR9多态性中，TLR2 2258 G>A SNP似乎是与波兰胎儿和新生儿先天性HCMV感染风险增加相关的重要因素。
Zotero 插件