| [PMID]: | 29248579 |
| [Au] Autor: | Girardelli M; Basaldella F; Paolera SD; Vuch J; Tommasini A; Martelossi S; Crovella S; Bianco AM |
| [Ad] Endereço: | Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", Via dell'istria 65, Trieste, Italy. |
| [Ti] Título: | Genetic profile of patients with early onset inflammatory bowel disease. |
| [So] Source: | Gene;645:18-29, 2018 Mar 01. |
| [Is] ISSN: | 1879-0038 |
| [Cp] País de publicação: | Netherlands |
| [La] Idioma: | eng |
| [Ab] Resumo: | Inflammatory Bowel disease (IBD) is a widespread pathological condition with clinical heterogeneity and with different levels of severity. Although IBD usually occurs in young adults, onset in childhood and infancy are described in patients within the 10th and second year of age. By genome-wide association studies and meta-analysis, several genetic loci have been identified associated with an increased risk of developing IBD in Western populations with variants that may alter the normal mucosal immunity in the gastrointestinal tract. The clinical complexity and the heterogeneity of the IBD phenotype probably reflect the presence of genetic heterogeneity where different genes or combinations of them may be involved, together with environmental factors. We hypothesized that patients with early onset IBD could have either more severe genetic variants in genes associated with IBD or multiple variants in different genes. Under the multifactorial diseases is crucial to consider the small contribution of a single variant in all not only to other small variations in the same gene but also in different genes belonging to the same pathway. We performed direct gene sequencing looking for 94 variations in NOD2, ATG16L1, IL23R, IL10R, IL10 and XIAP genes previously shown as correlated with IBD both in multifactorial and in Mendelian models. All variants identified are known in literature as being associated with IBD except for three variants in the genes NOD2, IL10 and IL10RB that even though present in online databases have never been involved in association studies on IBD patients. Moreover, we coupled genetic variants identification with an accurate "in silico" analysis to verify their predictive impact on the protein structure and function. The in-silico prediction of these variants results as benign therefore even if they exhibit a very low frequency in control population being benign, they cannot be considered pathogenic as monogenic disease but fall within the multifactorial range. The variants identified in our study partially reflect the association data described in the literature but there are no significant differences with the onset of disease (VEO vs EO-IBD). |
| [Mh] Termos MeSH primário: |
Predisposição Genética para Doença/genética
Doenças Inflamatórias Intestinais/genética
Polimorfismo de Nucleotídeo Único
Análise de Sequência de DNA/métodos
|
| [Mh] Termos MeSH secundário: |
Idade de Início
Proteínas Relacionadas à Autofagia/genética
Criança
Pré-Escolar
Simulação por Computador
Feminino
Estudo de Associação Genômica Ampla
Seres Humanos
Lactente
Interleucina-10/genética
Masculino
Proteína Adaptadora de Sinalização NOD2/genética
Receptores de Interleucina/genética
Receptores de Interleucina-10/genética
Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/genética
|
| [Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 0 (ATG16L1 protein, human); 0 (Autophagy-Related Proteins); 0 (IL10 protein, human); 0 (IL23R protein, human); 0 (NOD2 protein, human); 0 (Nod2 Signaling Adaptor Protein); 0 (Receptors, Interleukin); 0 (Receptors, Interleukin-10); 0 (X-Linked Inhibitor of Apoptosis Protein); 0 (XIAP protein, human); 130068-27-8 (Interleukin-10) |
| [Em] Mês de entrada: | 1801 |
| [Cu] Atualização por classe: | 180129 |
[Lr] Data última revisão:
| 180129 |
| [Sb] Subgrupo de revista: | IM |
| [Da] Data de entrada para processamento: | 171218 |
| [St] Status: | MEDLINE |
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