HLA class I and II and TNF-α gene polymorphisms in sarcoidosis patients
Estudo de polimorfismos genéticos do HLA (classes I e II) e do TNF-α em doentes com sarcoidose
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"https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S217351150870304X?idApp=UINPBA00004E" "url" => "/21735115/0000001400000006/v1_201305151501/S217351150870304X/v1_201305151501/en/main.assets" ] "en" => array:14 [ "idiomaDefecto" => true "titulo" => "HLA class I and II and TNF-α gene polymorphisms in sarcoidosis patients" "tieneTextoCompleto" => 0 "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "727" "paginaFinal" => "746" ] ] "autores" => array:1 [ 0 => array:3 [ "autoresLista" => "António Morais, Helena Alves, Bruno Lima, Luís Delgado, Ricardo Gonçalves, Sandra Tafulo" "autores" => array:6 [ 0 => array:3 [ "nombre" => "António" "apellidos" => "Morais" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">1</span>" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "Helena" "apellidos" => "Alves" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">2</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Bruno" "apellidos" => "Lima" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">2</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "Luís" "apellidos" => "Delgado" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">3</span>" "identificador" => "aff0015" ] ] ] 4 => array:3 [ "nombre" => "Ricardo" "apellidos" => "Gonçalves" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">2</span>" "identificador" => "aff0010" ] ] ] 5 => array:3 [ "nombre" => "Sandra" "apellidos" => "Tafulo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">2</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Serviço de Pneumologia do Hospital São João, Porto / Pulmonology Unit, Hospital São João, Porto" "etiqueta" => "<span class="elsevierStyleSup">1</span>" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Centro de Histocompatibilidade do Norte / Histocompatability Centre of the North" "etiqueta" => "<span class="elsevierStyleSup">2</span>" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Serviço de Imunologia da Faculdade de Medicina do Porto / Pulmonology Unit, Porto Faculty of Medicine" "etiqueta" => "<span class="elsevierStyleSup">3</span>" "identificador" => "aff0015" ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Estudo de polimorfismos genéticos do HLA (classes I e II) e do TNF-α em doentes com sarcoidose" ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2008-03-26" "fechaAceptado" => "2008-06-17" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Key-words" "identificador" => "xpalclavsec159791" "palabras" => array:3 [ 0 => "Sarcoidosis" 1 => "genetics" 2 => "HLA" ] ] ] "pt" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palavras-chave" "identificador" => "xpalclavsec159790" "palabras" => array:3 [ 0 => "Sacordoise" 1 => "genética" 2 => "HLA" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span class="elsevierStyleSectionTitle">Introduction</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Several factors suggest a genetic predisposition to sarcoidosis, namely the recognition of race as a risk factor and the occurrence of familial clustering of cases. Several studies have reported an association of sarcoidosis and HLA class I and especially class II alleles in different populations.</p> <span class="elsevierStyleSectionTitle">Aim</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">HLA class I, class II and TNF-α genotyping in a group of sarcoidosis patients and its relation with clinical presentation and outcome.</p> <span class="elsevierStyleSectionTitle">Material and methods</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">A total of 104 sarcoidosis patients were included. Clinical presentation, functional, radiology, BAL findings and organ involvement were studied. HLA– A<span class="elsevierStyleSup">*</span>, -B<span class="elsevierStyleSup">*</span>, -C<span class="elsevierStyleSup">*</span>, DRB1<span class="elsevierStyleSup">*</span>, DQB1<span class="elsevierStyleSup">*</span> and TNF-α were genotyped by molecular biology methods. DNA was extracted from peripheral blood and PCR-SSP and PCR-reverse hybridisation me-thods were used. Allele frequencies were compared with controls from the same region. The X2 test was used for discrete values and the Kruskal-Wallis test for continuous values.</p> <span class="elsevierStyleSectionTitle">Results</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">When patients were compared with controls we noticed increased frequencies of B<span class="elsevierStyleSup">*</span>08 (10.6% vs. 6.1%), O.R.<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1.8, C.I.<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>[1.1;3.1], p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.02; DRB1<span class="elsevierStyleSup">*</span>12 (4.3% vs. 1.7%), O.R.<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>2.63, C.I.<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>[1.1;6.1], p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.03. Patients with erythema nodosum have increased frequencies of the alleles DRB1<span class="elsevierStyleSup">*</span>03 (28% vs. 9.3%), R.R.<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>2.39, C.I.<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>[1.5;3.8], p<span class="elsevierStyleInf">c</span>=0.01 and DQB1<span class="elsevierStyleSup">*</span>02 (38% vs. 18%), R.R.<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>2.1, C.I.<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>[1.3;3.3], p<span class="elsevierStyleInf">c</span>=0.02. Allele DQB1<span class="elsevierStyleSup">*</span>03 is decreased in patients with obstructive pattern R.R.<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.53, C.I.<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>[0.3;0.9], p<span class="elsevierStyleInf">c</span>=0.05. Allele DRB1<span class="elsevierStyleSup">*</span>15 is related to restrictive pattern and reduced diffusion capacity (21.1% <span class="elsevierStyleItalic">vs</span>. 6.6%), R.R.<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>2.46, C.I.<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>[1.35;4.48], p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.01 and (18.1% <span class="elsevierStyleItalic">vs</span>. 3.8%), R.R.=1.87, p<span class="elsevierStyleInf">c</span>= 0.05 respectively. The TNF-α A/A (high) genotype is significantly associated with erythema nodosum (p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.04).</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">These data add support to the genetic association of HLA class I and II with sarcoidosis in terms of susceptibility, type of presentation, severity and outcome. Moreover as previously described in other populations, the TNF-α A/A (high) genotype has a significant association with erythema nodosum.</p>" ] "pt" => array:2 [ "titulo" => "Resumo" "resumen" => "<span class="elsevierStyleSectionTitle">Introdução</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A susceptibilidade genética na ocorrência da sarcoidose é sugerida por alguns factores, nomeadamente pela observação de casos de agregação familiar e a associação da raça a diferentes tipos de incidência e gravidade da doença. Vários estudos têm evidenciado a associação da classe I e especialmente da classe II do sistema HLA com a susceptibilidade à sarcoidose.</p> <span class="elsevierStyleSectionTitle">Objectivos</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Estudo dos polimorfismos genéticos da classe I e II do sistema HLA e do TNF-α num grupo de doentes com sarcoidose, nomeadamente a sua influência na susceptibilidade, apresentação clínica e evolução da doença.</p> <span class="elsevierStyleSectionTitle">Material e métodos</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Foram incluídos 104 doentes com sarcoidose, tendo sido estudadas a apresentação clínica, funcional, radiológica e os resultados do LBA. Foram usados métodos de biologia molecular na genotipagem do HLA -A<span class="elsevierStyleSup">*</span>, B<span class="elsevierStyleSup">*</span>, C<span class="elsevierStyleSup">*</span>, DRB1<span class="elsevierStyleSup">*</span>, DQB1<span class="elsevierStyleSup">*</span> e TNF -α. O ADN foi extraído do sangue periférico e foram usados os métodos PCR -SSP e PCR -<span class="elsevierStyleItalic">reverse hibridization</span>. As frequências alélicas foram comparadas com controlos da mesma região geográfica pelo teste χ<span class="elsevierStyleSup">2</span>, sendo usado o teste Kruskal-Wallis para variáveis contínuas.</p> <span class="elsevierStyleSectionTitle">Resultados</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Comparativamente com os controlos, os doentes incluídos apresentavam frequências aumentadas de: B<span class="elsevierStyleSup">*</span>08 (10,6% <span class="elsevierStyleItalic">vs</span> 6,1%), OR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1,8, IC=[1,1;3,1], p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,02; DRB1<span class="elsevierStyleSup">*</span>12 (4,3% <span class="elsevierStyleItalic">vs</span> 1,7%), OR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>2,63, IC<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>[1,1;6,1], p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,03. Os doentes com eritema nodoso apresentaram aumento das frequências alélicas de DRB1<span class="elsevierStyleSup">*</span>03 (28% <span class="elsevierStyleItalic">vs</span> 9,3%), RR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>2,39, IC<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>[1,5;3,8], p<span class="elsevierStyleInf">c</span>=0,01 e DQB1<span class="elsevierStyleSup">*</span>02 (38% vs 18%), RR=2,1, IC=[1,3;3,3], p<span class="elsevierStyleInf">c</span>=0,02. O alelo DQB1<span class="elsevierStyleSup">*</span>03 está diminuído nos doentes que apresentam síndroma ventilatória obstrutiva, RR=0,53, IC=[0,3;0,9], p<span class="elsevierStyleInf">c</span>=0,05. O alelo DRB1<span class="elsevierStyleSup">*</span>15 encontra -se significativamente associado quer à síndroma ventilatória restritiva quer à diminuição da transferência alveolocapilar (21,1% <span class="elsevierStyleItalic">vs</span> 6,6%), RR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>2,46, IC<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>[1,35;4,48], p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,01 e (18,1% <span class="elsevierStyleItalic">vs</span> 3,8%), RR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1,87, pc<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,05, respectivamente. Por sua vez, o genótipo A/A (<span class="elsevierStyleItalic">high</span>) do TNF -α apresentou uma frequência aumentada (p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,04) nos doentes com eritema nodoso.</p> <span class="elsevierStyleSectionTitle">Conclusões</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Os resultados obtidos adicionam evidência ao facto de, quer a classe I quer a classe II do sistema HLA influenciarem a susceptibilidade, o tipo de apresentação, o grau de gravidade e a evolução na sarcoidose. Por outro lado, o eritema nodoso parece relacionar -se com o genótipo de elevada produção de TNF -α, associação esta já anteriormente descrita.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "Bibliography/Bibliografia" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:42 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1." 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