Variations in maternal adenylate cyclase genes are associated with congenital Zika syndrome in a cohort from Northeast, Brazil

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dc.creatorÁ. D. Rossi
dc.creatorRenato Santana de Aguiar
dc.creatorCynthia Chester Cardoso
dc.creatorConstantine A. Stratakis
dc.creatorFabio Faucz
dc.creatorA. Melo
dc.creatorP. Pezzuto
dc.creatorG. S. de Azevedo
dc.creatorB. L. F. Schamber Reis
dc.creatorJ. S. Tavares
dc.creatorJ. J. Mattapallil
dc.creatorAmilcar Tanuri
dc.date.accessioned2023-07-17T17:32:49Z
dc.date.accessioned2025-09-08T23:46:08Z
dc.date.available2023-07-17T17:32:49Z
dc.date.issued2018
dc.identifier.doihttps://doi.org/10.1111/joim.12829
dc.identifier.issn0954-6820
dc.identifier.urihttps://hdl.handle.net/1843/56394
dc.languagepor
dc.publisherUniversidade Federal de Minas Gerais
dc.relation.ispartofJournal of Internal Medicine
dc.rightsAcesso Restrito
dc.subjectDoenças congenitas
dc.subjectDoenças infecciosas
dc.subjectVirologia
dc.subject.otherCongenital malformations
dc.subject.otherGene polymorphism
dc.subject.otherInfectious disease
dc.subject.otherVirology
dc.subject.otherZika
dc.titleVariations in maternal adenylate cyclase genes are associated with congenital Zika syndrome in a cohort from Northeast, Brazil
dc.typeArtigo de periódico
local.citation.spage123
local.citation.volume13
local.description.resumoBackground Vertical transmission of Zika virus (ZIKV) is associated with congenital malformations but the mechanism of pathogenesis remains unclear. Although host genetics appear to play a role, no genetic association study has yet been performed to evaluate this question. In order to investigate if maternal genetic variation is associated with Congenital Zika Syndrome (CZS), we conducted a case–control study in a cohort of Brazilian women infected with ZIKV during pregnancy. Methods A total of 100 women who reported symptoms of zika during pregnancy were enrolled and tested for ZIKV. Among 52 women positive for ZIKV infection, 28 were classified as cases and 24 as controls based on the presence or absence of CZS in their infants. Variations in the coding region of 205 candidate genes involved in cAMP signaling or immune response were assessed by high throughput sequencing and tested for association with development of CZS. Results From the 817 single nucleotide variations (SNVs) included in association analyses, 22 SNVs in 17 genes were associated with CZS under an additive model (alpha = 0.05). Variations c.319T>C (rs11676272) and c.1297G>A, located at ADCY3 and ADCY7 genes showed the most prominent effect. The association of ADCY3 and ADCY7 genes was confirmed using a Sequence Kernel Association Test to assess the joint effect of common and rare variations, and results were statistically significant after adjustment for multiple comparisons (P < 0.002). Conclusion These results suggest that maternal ADCY genes contribute to ZIKV pathogenicity and influence the outcome of CZS, being promising candidates for further replication studies and functional analysis.
local.identifier.orcidhttps://orcid.org/0000-0001-5180-3717
local.identifier.orcidhttps://orcid.org/0000-0002-4058-5520
local.identifier.orcidhttps://orcid.org/0000-0001-7959-9842
local.publisher.countryBrasil
local.publisher.departmentICB - INSTITUTO DE CIÊNCIAS BIOLOGICAS
local.publisher.initialsUFMG
local.url.externahttps://onlinelibrary.wiley.com/doi/10.1111/joim.12829

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