Genetic variation in toll like receptors 2, 7, 9 and interleukin-6 is associated with cytomegalovirus infection in late pregnancy

Abstract

Background: Maternal cytomegalovirus (CMV) infection and/or reactivation in pregnancy is associated with a myriad of adverse infant outcomes. However, the role of host genetic polymorphisms in modulating maternal CMV status is inconclusive. This study investigated the possible association of single nucleotide polymorphisms in toll-like receptor (TLR) and cytokine genes with maternal plasma CMV DNA status in black Zimbabweans. Methods: In a cross-sectional study, 110 women in late gestation who included 36 CMV infected cases and 74 CMV uninfected, age and HIV status matched controls were enrolled. Twenty single nucleotide polymorphisms in 10 genes which code for proteins involved in immunity against CMV were genotyped using Iplex GOLD SNP genotyping protocol on the Agena MassARRAY® system. Statistical analyses were performed using Stata SE and the 'Genetics' and 'SNPassoc' packages of the statistical package R. Results: The TLR7 rs179008A > T (p < 0.001) polymorphism was associated while the TLR9 rs352139T > C (p = 0.049) polymorphism was on the borderline for association with CMV positive (CMV+) status. In contrast, the interleukin (IL)-6 rs10499563T > C (p < 0.001) and TLR2 rs1816702C > T (p = 0.001) polymorphisms were associated with CMV negative (CMV-) status. Furthermore, allele frequencies of SNPs in TLR2, TLR4, TLR9, TLR7, IL-6, IL-10, IL-28B, IL-1A and interferon AR1 (IFNAR1) genes are being reported here for the first time in a Zimbabwean population. The allele frequencies in the Zimbabwean population are generally comparable to other African populations but different when compared to European and Asian populations. Conclusions: Toll-like receptor and interleukin genetic polymorphisms influence CMV status in late gestation among black Zimbabweans. This is attributable to possible modulation of immune responses to CMV reactivation in a population previously exposed to CMV infection.

The Limitations of Cytomegalovirus DNA Detection in Cerebrospinal Fluid of Newborn Infants With Congenital CMV Infection: A Tertiary Care Neonatal Center Experience

“…On the other hand, no variation in the TLR4 genes was associated with the development of symptomatic acquired CMV infection in adults, 40 including primary and nonprimary CMV infection in pregnant women. 41 Finally, the higher viral load in blood in the positive CSF-CMV-PCR infants might be speculated as an additional predisposing factor of CNS involvement. However, we found no association between TLR4 SNPs and viral load in blood and urine in infants with cCMV infection in our previous study.…”

“…On the other hand, no variation in the TLR4 genes was associated with the development of symptomatic acquired CMV infection in adults, 40 including primary and nonprimary CMV infection in pregnant women. 41…”