Variations in maternal adenylate cyclase genes are associated with congenital Zika syndrome in a cohort from Northeast, Brazil
| Autor: | Paula Pezzuto, Jousilene de Sales Tavares, Amilcar Tanuri, Fabio R. Faucz, G S de Azevedo, Renato S. Aguiar, Áurea Nogueira de Melo, Átila Duque Rossi, Bruno Luiz Fonseca Schamber-Reis, Cynthia Chester Cardoso, J J Mattapallil, C. A. Stratakis |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Candidate gene DNA Mutational Analysis 030204 cardiovascular system & hematology Article Zika virus 03 medical and health sciences 0302 clinical medicine Pregnancy Genetic variation Internal Medicine Medicine Humans Pregnancy Complications Infectious Genetic association Retrospective Studies Genetics biology business.industry Zika Virus Infection Incidence Zika Virus ADCY3 biology.organism_classification medicine.disease 030104 developmental biology Cohort DNA Viral Mutation Female Gene polymorphism business Brazil Adenylyl Cyclases Follow-Up Studies |
| ISSN: | 1167-6272 |
| Popis: | Rossi ÁD, Faucz FR, Melo A, Pezzuto P, de Azevedo GS, Schamber-Reis BLF, Tavares JS, Mattapallil JJ, Tanuri A, Aguiar RS, Cardoso CC, Stratakis CA (Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; National Institutes of Health, Bethesda, MD, USA; Instituto de Pesquisa Professor Joaquim Amorim Neto; Centro Universitário UniFacisa, Campina Grande, Brazil; Uniformed Services University, Bethesda, MD, USA). Variations in maternal adenylate cyclase genes are associated with congenital Zika syndrome in a cohort from Northeast, Brazil. J Intern Med 2018; https://doi.org/10.1111/joim.12829 BACKGROUND. 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. |
| Databáze: | OpenAIRE |
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