Contribution of miR-124 rs531564 polymorphism to the occurrence of congenital Zika syndrome

Abstract

Zika virus (ZIKV) cause Congenital Zika Syndrome (CZS) in individuals exposed during pregnancy. Studies have shown that ZIKV infection positively regulates the miR-124 expression in neural cells, which leads to a decrease of TFRC, a gene targeted of this miRNA. Both miR-124 and TFRC exhibit a pivotal role in nervous system development. Therefore, in this study we aimed to investigate whether genetic variants that affect the expression of these genes could act together with ZIKV to increase the risk of individuals developing CZS. TFRC rs406271 and MIR-124-1 rs531564 polymorphisms were genotyped, using TaqMan® Genotyping Assays, in a sample of children who were exposed to ZIKV during pregnancy, of whom 40 were born with CZS and 48 without congenital anomalies. We identified that individuals with CZS presented a higher frequency of CG genotype of rs531564 polymorphism in MIR-124-1 (p=0.048), which is associated with increased expression of miR-124. Since ZIKV also upregulates the expression of this miRNA, the presence of CG genotype in individuals exposed to the virus could lead to a scenario of overexpression of miR-124 in the brain. Since teratogenesis is a multifactorial event, this genetic finding could partly explain why such individuals are more susceptible to CZS, considering both the downregulation of important neurodevelopment genes, as well as deregulation of the neurogenesis process. Thus, we provide preliminary evidence about a possible genetic risk factor to CZS and highlight the importance of analyzing functional polymorphisms related to epigenetic modulators of neurodevelopment genes in the context of ZIKV teratogenesis.

Investigation of the impact of AXL, TLR3, and STAT2 in congenital Zika syndrome through genetic polymorphisms and protein–protein interaction network analyses

“…So far, very few studies have investigated the role of common genetic variants on the susceptibility to congenital anomalies induced by ZIKV. Such studies linked some variants as possibly risk factors to this condition (Azamor et al, 2021; Gomes et al, 2021; Gomes et al, 2023; Gullo et al, 2022; Santos et al, 2023). Based on reports from these studies about key genes and proteins involved in ZIKV infection and teratogenesis, this study aimed to evaluate the role of functional genetic variants in three of the most investigated genes— AXL , TLR3 , and STAT2 —as candidates for the susceptibility to ZIKV teratogenesis and, consequently, the development of the CZS.…”

Auditory Neural Responses and Communicative Functioning in Children With Microcephaly Related to Congenital Zika Syndrome

“…In Maceió, a region with fewer resources, when RT-PCR testing was not available, the history of maternal ZIKV infection was determined based on established epidemiologic criteria: presence of symptoms during pregnancy (e.g., rash, fever, headache, myalgia, edema, skin pruritus, red eyes), residing in an area linked to ZIKV, negative test results for other infections (syphilis, toxoplasmosis, rubella, cytomegalovirus, and herpes simplex, dengue, chikungunya). These criteria have been successfully used in other clinical studies (Fandiño-Cárdenas et al 2018; Gomes et al 2023) to identify children with prenatal ZIKV exposure. In the present sample, PCR confirmation was available for 12 children.…”