Increased expression of IL12B mRNA transcribed from the risk haplotype for Crohn’s disease is a risk factor for disease relapse in Japanese patients
| Autor: | Tooru Shimosegawa, Tomoya Kimura, Yoshitaka Kinouchi, Kenichi Negoro, Katsuya Endo, Hisashi Shiga, Masatake Kuroha, Yoichi Kakuta |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
Male 0301 basic medicine Adolescent Genotype Single-nucleotide polymorphism Biology Polymorphism Single Nucleotide Young Adult 03 medical and health sciences Crohn Disease Japan Recurrence Risk Factors Humans SNP Genetic Predisposition to Disease RNA Messenger Risk factor Allele Alleles Interleukin-12 Subunit p40 Haplotype Gastroenterology Case-control study Phenotype 030104 developmental biology Haplotypes Case-Control Studies Immunology Colitis Ulcerative Female Candidate Gene Analysis |
| Zdroj: | Journal of Gastroenterology. 52:1230-1239 |
| ISSN: | 1435-5922 0944-1174 |
| DOI: | 10.1007/s00535-017-1322-5 |
| Popis: | IL12B is a promising candidate for a susceptibility gene in Crohn’s disease (CD). The aim of this study was to perform a candidate gene analysis of IL12B in Japanese CD patients, investigate whether the genotype is associated with disease phenotypes, and determine how the risk allele affects susceptibility to CD. Three hundred seventy-five patients with CD, 265 patients with ulcerative colitis, and 463 healthy controls were examined. Ten single-nucleotide polymorphisms (SNPs) around IL12B were genotyped. Case–control and subphenotype (including disease course) analyses were performed. The allelic expression ratio of IL12B messenger RNA (mRNA) was examined by a SNaPshot analysis in lipopolysaccharide-stimulated monocytes. Four SNPs located upstream of the IL12B gene were significantly associated with CD. A conditional analysis revealed that these associations included two independent signals tagged by IL12B_1 and IL12B_3 (P = 9.42 × 10−6 and 1.49 × 10−4 respectively). IL12B_3 was also associated with earlier relapse in CD (P = 0.0144). The allelic expression ratios of IL12B mRNA transcribed from the risk haplotype to the protective haplotype tagged by IL12B_3 in lipopolysaccharide-stimulated monocytes from ten healthy controls heterozygous for IL12B_3 were significantly higher than that of the respective genomic DNA (P = 0.00923). No SNP was associated with ulcerative colitis. We confirmed the association of SNPs located upstream of IL12B with CD in Japanese patients. The demonstrated allelic expression imbalance supports the idea that the IL12B risk haplotype confers susceptibility not only to CD onset but to also relapse through increased IL12B mRNA expression. |
| Databáze: | OpenAIRE |
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