ArticlePloS one2012
Analysis of IL12B gene variants in inflammatory bowel disease.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 3 of them syntheses that pooled it.
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Who cites it
31 citing papers in PubMed, 3 syntheses or guidelines pooled it, 58 citations in OpenAlex.
- A systematic review and functional bioinformatics analysis of genes associated with Crohn's disease identify more than 120 related genes.BMC genomics · 2022Pooled it
- Interleukin and interleukin receptor gene polymorphisms in inflammatory bowel diseases susceptibility.World journal of gastroenterology · 2014Pooled it
- Pooled it
- Towards Precision Medicine in Inflammatory Bowel Diseases: Pharmacogenetic Predictors of Ustekinumab Effectiveness and Persistence.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Article
- Correlation analysis of serum levels of H19 and CRP levels and ulcerative colitis.Journal of medical biochemistry · 2023Article
- Multi-phasic gene profiling using candidate gene approach predict the capacity of specific antibody production and maintenance following COVID-19 vaccination in Japanese population.Frontiers in immunology · 2023Article
- Evidence of a genetically driven metabolomic signature in actively inflamed Crohn's disease.Scientific reports · 2022Article
- Long-Term Dietary Patterns Are Reflected in the Plasma Inflammatory Proteome of Patients with Inflammatory Bowel Disease.Nutrients · 2022Article
- The Effect of Phenotype and Genotype on the Plasma Proteome in Patients with Inflammatory Bowel Disease.Journal of Crohn's & colitis · 2022Article
- Cow Milk Extracellular Vesicle Effects on an In Vitro Model of Intestinal Inflammation.Biomedicines · 2022Article
- Metabolic Host-Microbiota Interactions in Autophagy and the Pathogenesis of Inflammatory Bowel Disease (IBD).Pharmaceuticals (Basel, Switzerland) · 2021Review
- Genome-Wide DNA Methylation Changes Associated With High-Altitude Acclimatization During an Everest Base Camp Trek.Frontiers in physiology · 2021Article
- Interleukin-12B gene rs6887695 and rs2288831 polymorphisms are associated with an increased risk of ulcerative colitis development in Chinese Han population: A case-control study.Journal of clinical laboratory analysis · 2020Article
- Article
- Article
- An integrative network-based approach to identify novel disease genes and pathways: a case study in the context of inflammatory bowel disease.BMC bioinformatics · 2018Article
- Effector T Helper Cell Subsets in Inflammatory Bowel Diseases.Frontiers in immunology · 2018Review
- A blood-based biomarker panel indicates IL-10 and IL-12/23p40 are jointly associated as predictors of β-amyloid load in an AD cohort.Scientific reports · 2017Article
- A functional IL1RL1 variant regulates corticosteroid-induced sST2 expression in ulcerative colitis.Scientific reports · 2017Observational
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIL12B encodes the p40 subunit of IL-12, which is also part of IL-23. Recent genome-wide association studies identified IL12B and IL23R as susceptibility genes for inflammatory bowel disease (IBD). However, the phenotypic effects and potential gene-gene interactions of IL12B variants are largely unknown. METHODOLOGY/PRINCIPAL
findingsWe analyzed IL12B gene variants regarding association with Crohn's disease (CD) and ulcerative colitis (UC). Genomic DNA from 2196 individuals including 913 CD patients, 318 UC patients and 965 healthy, unrelated controls was analyzed for four SNPs in the IL12B gene region (rs3212227, rs17860508, rs10045431, rs6887695). Our analysis revealed an association of the IL12B SNP rs6887695 with susceptibility to IBD (p = 0.035; OR 1.15 [95% CI 1.01-1.31] including a trend for rs6887695 for association with CD (OR 1.41; [0.99-1.31], p = 0.066) and UC (OR 1.18 [0.97-1.43], p = 0.092). CD patients, who were homozygous C/C carriers of this SNP, had significantly more often non-stricturing, non-penetrating disease than carriers of the G allele (p = 6.8×10(-5); OR = 2.84, 95% CI 1.66-4.84), while C/C homozygous UC patients had less often extensive colitis than G allele carriers (p = 0.029; OR = 0.36, 95% CI 0.14-0.92). In silico analysis predicted stronger binding of the minor C allele of rs6887695 to the transcription factor RORα which is involved in Th17 differentiation. Differences regarding the binding to the major and minor allele sequence of rs6887695 were also predicted for the transcription factors HSF1, HSF2, MZF1 and Oct-1. Epistasis analysis revealed weak epistasis of the IL12B SNP rs6887695 with several SNPs (rs11889341, rs7574865, rs7568275, rs8179673, rs10181656, rs7582694) in the STAT4 gene which encodes the major IL-12 downstream transcription factor STAT4 (p<0.05) but there was no epistasis between IL23R and IL12B variants. CONCLUSIONS/SIGNIFICANCE: The IL12B SNP rs6887695 modulates the susceptibility and the phenotype of IBD, although the effect on IBD susceptibilty is less pronounced than that of IL23R gene variants.
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