Abstract
Congenital Zika syndrome (CZS) is characterized by a diverse group of congenital malformations induced by ZIKV infection during pregnancy. Type III interferons have been associated with placental immunity against ZIKV and restriction of vertical transmission in mice, and non-coding single-nucleotide polymorphisms (SNPs) on these genes are well known to influence susceptibility to other viral infections. However, their effect on ZIKV pathogenesis has not yet been explored. To investigate whether maternal non-coding SNPs at IFNL genes are associated with CZS, 52 women infected with ZIKV during pregnancy were enrolled in a case–control association study. A total of 28 women were classified as cases and 24 as controls based on the presence or absence of CZS in their infants, and seven Interferon-λ non-coding SNPs (rs12980275, rs8099917, rs4803217, rs4803219, rs8119886, rs368234815, rs12979860) were genotyped. The results of logistic regression analyses show an association between the G allele at rs8099917 and increased susceptibility to CZS under a log-additive model (adjustedOR = 2.80; 95%CI = 1.14–6.91; p = 0.02), after adjustment for trimester of infection and genetic ancestry. These results provide evidence of an association between Interferon-λ SNPs and CZS, suggesting rs8099917 as a promising candidate for further studies on larger cohorts.
Highlights
Zika fever is an arthropod-borne viral disease transmitted mostly by Aedes mosquitoes’bites, alternative routes such as transfusion and vertical transmission have been described [1,2]
Subjects were classified as cases (n = 28) based on the presence of neurological congenital malformations such as microcephaly, brain calcifications, ventriculomegaly, cerebellar hypoplasia, arthrogryposis, lissencephaly and/or hydrocephaly due to ZIKV infection in infants
To investigate whether maternal Interferon-λ genes are associated with Congenital Zika syndrome (CZS), we conducted a case–control association study considering 7 single-nucleotide polymorphisms (SNPs) in 52 women from the Northeast region of Brazil
Summary
Zika fever is an arthropod-borne viral disease transmitted mostly by Aedes mosquitoes’. Bites, alternative routes such as transfusion and vertical transmission have been described [1,2]. Infection by Zika virus (ZIKV) is, in general, self-limiting and asymptomatic, but mild symptoms such as fever, myalgia, arthralgia, rash and conjunctivitis may be present [2]. ZIKV-infected individuals may develop an autoimmune outcome: 4.0/). Most of the ZIKV burden relates to severe outcomes observed after vertical transmission events, known as congenital Zika syndrome (CZS). CZS harbors different neurological congenital malformations that may include microcephaly, ocular anomalies, arthrogryposis, lissencephaly, hydrocephaly, brain calcifications and postnatal neurodevelopmental impairment [2]. About 4 to 8% of children born from women infected with ZIKV exhibit malformations, suggesting that additional risk factors are required for the CZS outcome [4]. Preliminary results of a comparative twin study have suggested that
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