{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T15:22:32Z","timestamp":1767626552737,"version":"3.40.5"},"reference-count":42,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2018,9,21]],"date-time":"2018-09-21T00:00:00Z","timestamp":1537488000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","award":["2016\/02667\u20100"],"award-info":[{"award-number":["2016\/02667\u20100"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environ and Mol Mutagen"],"published-print":{"date-parts":[[2019,3]]},"abstract":"<jats:p>During development, oxidative stress is hypothesized to mediate embryotoxicity, which may be intensified by exposition to environmental factors and by genetic variations in the enzymes involved in protecting cells from these damaging effects, including superoxide dismutase (<jats:italic>SOD<\/jats:italic>) and paraoxonase (<jats:italic>PON<\/jats:italic>). The aim of this study was to evaluate the influence of single\u2010nucleotide polymorphisms (SNP) in genes associated with the neutralization of oxidative stress (<jats:italic>SOD<\/jats:italic> and <jats:italic>PON<\/jats:italic> family members) in the risk of nonsyndromic oral cleft in the Brazilian population. Initially, we tested for association between 28 SNP in <jats:italic>SOD1<\/jats:italic>, <jats:italic>SOD2<\/jats:italic>, <jats:italic>SOD3<\/jats:italic>, <jats:italic>PON1<\/jats:italic>, <jats:italic>PON2,<\/jats:italic> and <jats:italic>PON3<\/jats:italic> among 325 nonsyndromic cleft lip with or without cleft palate (NSCL\u00b1P) case\u2010parent trios. Multiple logistic regression analyses were used to explore gene, GxG and GxE, involving factors that induce oxidative stress accumulation during pregnancy. Signals still significant after both Bonferroni correction and in permutation test were subsequently confirmed in an ancestry\u2010structured case\u2013control analysis with 722 NSCL\u00b1P and 866 controls from the same population. In the trio sample, transmission disequilibrium test (TDT) (allele and haplotype) and GxE analysis showed no significant associations, but multiple pairwise GxG interactions involving 10 SNP in <jats:italic>PON1<\/jats:italic>, <jats:italic>PON2,<\/jats:italic> and <jats:italic>PON3<\/jats:italic> were detected and further examined in the case\u2013control sample. The <jats:italic>PON1<\/jats:italic> rs2237583 and <jats:italic>PON2<\/jats:italic> rs17166879 yielded significant evidence of SNP\u2010SNP interactions after adjustment for multiple tests (both Bonferroni correction and 10,000 permutation test). The C allele and the CT genotype of <jats:italic>PON1<\/jats:italic> rs2237583 were associated with significant protective effects against NSCL\u00b1P, while rs3917490 showed a significant association only in the sample composed of patients displaying high African ancestry. Our results reveal associations between rs2237583 and rs3917490 in <jats:italic>PON1<\/jats:italic> and GxG interactions containing rs2237583 and rs17166879 with the susceptibility of NSCL\u00b1P in the Brazilian population. Furthermore, this study underlines the recent tendency of taking into account potential GxG interactions to clarify the underlying mechanisms associated with the etiology of this common malformation. Environ. Mol. Mutagen. 60: 185\u2013196, 2019. \u00a9 2018 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/em.22239","type":"journal-article","created":{"date-parts":[[2018,9,22]],"date-time":"2018-09-22T09:25:16Z","timestamp":1537608316000},"page":"185-196","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Interactions between superoxide dismutase and paraoxonase polymorphic variants in nonsyndromic cleft lip with or without cleft palate in the Brazilian population"],"prefix":"10.1002","volume":"60","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1697-3662","authenticated-orcid":false,"given":"Renato Assis","family":"Machado","sequence":"first","affiliation":[{"name":"Department of Oral Diagnosis, School of Dentistry University of Campinas  Piracicaba S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolina","family":"de Oliveira Silva","sequence":"additional","affiliation":[{"name":"Department of Oral Diagnosis, School of Dentistry University of Campinas  Piracicaba S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darlene Camati","family":"Persuhn","sequence":"additional","affiliation":[{"name":"Molecular Biology Department Federal University of Paraiba  Jo\u00e3o Pessoa Paraiba Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vanessa","family":"de Melo Cavalcanti Dantas","sequence":"additional","affiliation":[{"name":"Molecular Biology Department Federal University of Paraiba  Jo\u00e3o Pessoa Paraiba Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia Regina","family":"de Almeida Reis","sequence":"additional","affiliation":[{"name":"Department of Basic Science Bahiana School of Medicine and Public Health  Salvador Bahia 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