{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1363670318928089216.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1017/cts.2019.3"}},{"identifier":{"@type":"URI","@value":"https://www.cambridge.org/core/services/aop-cambridge-core/content/view/S2059866119000037"}}],"dc:title":[{"@value":"Identification of functional missense single-nucleotide polymorphisms in <i>TNFAIP3</i> in a predominantly Hispanic population"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:title>Abstract</jats:title><jats:sec id=\"S2059866119000037_as1\"><jats:title>Background:</jats:title><jats:p>Tumor necrosis factor alpha-induced protein 3 (<jats:italic>TNFAIP3</jats:italic>) is a multifunctional ubiquitin binding and editing enzyme that regulates inflammation. Genetic studies have implicated polymorphisms within the <jats:italic>TNFAIP3</jats:italic> locus to the development of numerous immune-related diseases. This study evaluated the frequencies of single-nucleotide polymorphism (SNPs) within the exonic regions of the <jats:italic>TNFAIP3</jats:italic> gene and an associated point mutation from the Illumina array among a predominantly Hispanic cohort.</jats:p></jats:sec><jats:sec id=\"S2059866119000037_as2\"><jats:title>Methods:</jats:title><jats:p>Genomic DNA was obtained from 721 participants and sequencing of all <jats:italic>TNFAIP3</jats:italic> exons and an intergenic point mutation (rs6920220) was performed. <jats:italic>In-vitro</jats:italic> functional assessment was performed by transfecting mutated <jats:italic>TNFAIP3</jats:italic> constructs into <jats:italic>TNFAIP3</jats:italic> knockout cells containing the NF-kB luciferase reporter and stimulating with TNFα. Comparative statistics were performed with Student’s <jats:italic>t</jats:italic>-test for continuous variables and chi-squared test for categorical variables.</jats:p></jats:sec><jats:sec id=\"S2059866119000037_as3\"><jats:title>Results:</jats:title><jats:p>Sequencing revealed two missense SNPs, rs146534657:A>G and rs2230926:T>G, both within exon 3 of <jats:italic>TNFAIP3</jats:italic>, which encodes the protein’s deubiquitinating enzymatic domain. Frequencies of all three point mutations differed significantly across racial groups (<jats:italic>χ</jats:italic><jats:sup>2</jats:sup>-test, <jats:italic>P</jats:italic> = 0.014 to <jats:italic>P</jats:italic> < 0.001). Compared to Caucasians, rs146534657:A>G was overrepresented among Hispanics (odds ratio (OR) [95% CI] 4.05 [1.24−13.18]), and rs2230926:T>G was more prevalent among African-Americans (OR [95% CI] 3.65 [1.58−8.43]). <jats:italic>In-vitro</jats:italic> assays confirm rs146534657:A>G and rs2230926:T>G decrease the ability of <jats:italic>TNFAIP3</jats:italic> to abrogate NF-κB activation by 2-fold (<jats:italic>P</jats:italic> < 0.01) and 1.7-fold (<jats:italic>P</jats:italic> < 0.01), respectively.</jats:p></jats:sec><jats:sec id=\"S2059866119000037_as4\"><jats:title>Conclusions:</jats:title><jats:p>This study reports the frequency of rs146534657:A>G among Hispanics and is the first to evaluate its potential physiologic impact, establishing a basis for future research as a potential biomarker among this population.</jats:p></jats:sec>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1383670318928089222","@type":"Researcher","foaf:name":[{"@value":"Bing Zhang"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318928089217","@type":"Researcher","foaf:name":[{"@value":"Brooke Naomi Nakamura"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318928089218","@type":"Researcher","foaf:name":[{"@value":"Aryeh Perlman"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318928089216","@type":"Researcher","foaf:name":[{"@value":"Omeed Alipour"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318928089224","@type":"Researcher","foaf:name":[{"@value":"Sadeea Qureshi Abbasi"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318928089223","@type":"Researcher","foaf:name":[{"@value":"Peter Sohn"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318928089226","@type":"Researcher","foaf:name":[{"@value":"Alakh Gulati"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318928089225","@type":"Researcher","foaf:name":[{"@value":"Graham Moore"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318928089227","@type":"Researcher","foaf:name":[{"@value":"Caroline Hwang"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318928089219","@type":"Researcher","foaf:name":[{"@value":"Sarah Sheibani"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318928089220","@type":"Researcher","foaf:name":[{"@value":"Thomas Zarchy"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318928089221","@type":"Researcher","foaf:name":[{"@value":"Ling Shao"}]}],"publication":{"publicationIdentifier":[{"@type":"EISSN","@value":"20598661"}],"prism:publicationName":[{"@value":"Journal of Clinical and Translational Science"}],"dc:publisher":[{"@value":"Cambridge University Press (CUP)"}],"prism:publicationDate":"2018-12","prism:volume":"2","prism:number":"6","prism:startingPage":"350","prism:endingPage":"355"},"reviewed":"false","dc:rights":["http://creativecommons.org/licenses/by-nc-nd/4.0/"],"url":[{"@id":"https://www.cambridge.org/core/services/aop-cambridge-core/content/view/S2059866119000037"}],"createdAt":"2019-05-14","modifiedAt":"2019-06-17","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360009142795071360","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Functional analysis of novel A20 variants in patients with atypical inflammatory diseases"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1017/cts.2019.3"},{"@type":"CROSSREF","@value":"10.1186/s13075-021-02434-w_references_DOI_C3XTtt0tamd3P6aTAqJmoKoxQzf"}]}