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Abstract
Congenital cytomegalovirus infection (cCMV) is the most common intrauterine infection with central nervous system (CNS) involvement. There is limited data on the associations between Single Nucleotide Polymorphisms (SNPs) in genes involving the first-line defense mechanism and the risk of CNS damage during cCMV. We investigated the associations between neuroimaging findings and SNPs in genes encoding the following cytokines and cytokine receptors in 92 infants with cCMV: interleukins (IL1B rs16944, IL12B rs3212227, IL28B rs12979860), C-C motif chemokine ligand 2 (CCL2 rs1024611), dendritic cell-specific intercellular adhesion grabbing non-integrin (DC-SIGN rs735240), Toll-like receptors (TLR2 rs5743708, TLR4 rs4986791, TLR9 rs352140). The SNP of IL1B rs16944 (G/A) was associated with a reduced risk of ventriculomegaly on MRI (OR = 0.46, 95% CI, 0.22–0.95; p = 0.03) and cUS (OR = 0.38, 95% CI, 0.0–0.93; p = 0.034). Infants carrying heterozygous (T/C) genotype at IL28B rs12979860 had an increased risk of cystic lesions on cUS (OR = 3.31, 95% CI, 1.37–8.01; p = 0.0064) and MRI (OR = 4.97, 95% CI, 1.84–13.43; p = 0.001), and an increased risk of ventriculomegaly on MRI (OR = 2.46, 95% CI, 1.03–5.90; p = 0.04). No other associations between genotyped SNPs and neuroimaging results were found. This is the first study demonstrating new associations between SNPs of IL1B and IL28B and abnormal neuroimaging in infants with cCMV.
Highlights
The objective of the study was to evaluate the association between Single Nucleotide Polymorphisms (SNPs) in eight candidate genes with a plausible contribution to Congenital cytomegalovirus infection (cCMV) disease and neuroimaging results in newborns with cCMV
In our earlier study [57], we found no associations between neonatal viral load and eight SNPs
As far as other tested SNPs are concerned, we would like to highlight TLRs and their role in cCMV, we found no association between the SNPs of TLR2, TLR4 or TLR9 and the abnormal neuroimaging results
Summary
Congenital human cytomegalovirus infection (cCMV) is the most common intrauterine infection. Human cytomegalovirus (HCMV) transmitted through placenta to immature fetus can lead to serious central nervous system (CNS) damage and sensorineural hearing loss (SNHL), with a long term and unfavorable sequelae [1,2]. The neurotropism of HCMV is evident from the predominance of CNS abnormalities observed in fetuses and neonates with cCMV [1,3,4]. HCMV may infect a wide spectrum of cell types, including neurons, astrocytes, radial glia, and endothelial cells, and may disrupt neuronal proliferation, migration, and cortical cell organization [1,5]. A higher number of infected cytomegalic cells, and a loss of germinal and radial glial cells in periventricular regions, is detected in the brains of infants with severe cCMV [6]. While an ultrasound (US) is the method of choice for fetal and neonatal imaging, magnetic resonance imaging (MRI)
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