Cytokine gene polymorphism associations with congenital cytomegalovirus infection and sensorineural hearing loss

B Kasztelewicz,J Romańska,J Czech-Kowalska,M K Borszewska-Kornacka,B Lipka,K Dzierżanowska-Fangrat,B Milewska-Bobula

doi:10.1007/s10096-017-2996-6

Abstract

Cytomegalovirus (CMV) is the most common viral agent of congenital infections and a leading nongenetic cause of sensorineural hearing loss (SNHL). The host immunologic factors that render a developing foetus prone to intrauterine CMV infection and development of hearing loss are unknown. The aim of this study was to assess the potential associations between the polymorphisms within cytokine and cytokine receptors genes, and the risk of congenital CMV infection, and the hearing outcome. A panel of 11 candidate single nucleotide polymorphisms (SNPs): TNF rs1799964, TNF rs1800629, TNFRSF1A rs4149570, IL1B rs16944, IL1B rs1143634, IL10 rs1800896, IL10RA rs4252279, IL12B rs3212227, CCL2 rs1024611, CCL2 rs13900, CCR5 rs333 was genotyped in 470 infants (72 with confirmed intrauterine CMV infection and 398 uninfected controls), and related to congenital CMV infection, and the outcome. In multivariate analysis, the IL1B rs16944 TT and TNF rs1799964 TC genotypes were significantly associated with intrauterine CMV infection (aOR = 2.32; 95% CI, 1.11–4.89; p = 0.032, and aOR = 2.17, 95% CI, 1.25–3.77; p = 0.007, respectively). Twenty-two out of 72 congenitally infected newborns had confirmed SNHL. Carriers of CT or TT genotype of CCL2 rs13900 had increased risk of hearing loss at birth and at 6 months of age (aOR = 3.59; p = 0.028 and aOR = 4.10; p = 0.039, respectively). This is the first study to report an association between SNPs in IL1B, TNF, and CCL2, and susceptibility to congenital CMV infection (IL1B and TNF) and SNHL (CCL2).

Highlights

Human cytomegalovirus (CMV) is a ubiquitous herpes virus
When genotype distributions in infants with congenital CMV infection were compared with uninfected controls, significant associations for IL1B rs16944 (IL1B -511 C/T) and TNF rs1799964 (−1031 C/T) polymorphisms were found (Table 3)
The rare IL1B −511 TT genotype was overrepresented in infants with congenital CMV infection compared to controls (OR = 2.52; 95% confidence intervals (CIs), 1.25–5.08; p = 0.014)

Summary

Introduction

In the majority of healthy adults and children primary infection is asymptomatic, but CMV is an important cause of morbidity and mortality in immunocompromised individuals, and the most common cause of congenital infection worldwide, with a birth prevalence of 0.64% [1]. Outcomes following congenital CMV infection are variable, ranging from asymptomatic infection and multiple organ involvement to stillbirth or death in the early neonatal period. Only 10% of congenitally-infected neonates have obvious clinical signs at birth, approximately two-thirds of them have permanent neurologic sequelae [4, 5]. Sensorineural hearing loss (SNHL) is the most common sequel following congenital CMV infection, affecting half of the symptomatic and 10–15% of the asymptomatic infants [6]. Diagnosis and prompt intervention (i.e. treatment and rehabilitation) can reduce the long-term sequelae in

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