The NOD2-Smoking Interaction in Crohn's Disease is likely Specific to the 1007fs Mutation and may be Explained by Age at Diagnosis: A Meta-Analysis and Case-Only Study

M Ellen Kuenzig, Jeff Yim, Stephanie Coward, Bertus Eksteen, Cynthia H Seow, Cheryl Barnabe, Herman W Barkema, Mark S Silverberg, Peter L Lakatos, Paul L Beck, Richard Fedorak, Levinus A Dieleman, Karen Madsen, Remo Panaccione, Subrata Ghosh, Gilaad G Kaplan

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Abstract

BACKGROUND: NOD2 and smoking are risk factors for Crohn's disease. We meta-analyzed NOD2-smoking interactions in Crohn's disease (Phase 1), then explored the effect of age at diagnosis on NOD2-smoking interactions (Phase 2).

METHODS: Phase 1: MEDLINE and EMBASE were searched for studies (n=18) providing data on NOD2 and smoking in Crohn's disease. NOD2-smoking interactions were estimated using odds ratios (ORs) and 95% confidence intervals (CIs) calculated using random effects models. Phase 2: A case-only study compared the proportion of smokers and carriers of the 1007fs variant across ages at diagnosis (≤16, 17-40, >40years).

FINDINGS: Phase 1: Having ever smoked was less common among carriers of the 1007fs variant of NOD2 (OR 0.74, 95%CI:0.66-0.83). There was no interaction between smoking and the G908R (OR 0.96, 95%CI:0.82-1.13) or the R702W variant (OR 0.89, 95%CI:0.76-1.05). Phase 2: The proportion of patients (n=627) carrying the 1007fs variant decreased with age at diagnosis (≤16years: 15%; 17-40: 12%; >40: 3%; p=0.003). Smoking was more common in older patients (≤16years: 4%; 17-40: 48%; >40: 71%; p<0.001).

INTERPRETATION: The negative NOD2-smoking interaction in Crohn's disease is specific to the 1007fs variant. However, opposing rates of this variant and smoking across age at diagnosis may explain this negative interaction.

Original languageEnglish
Pages (from-to)188-196
Number of pages9
JournalEBioMedicine
Volume21
Early online date16 Jun 2017
DOIs
Publication statusPublished - Jul 2017

Keywords

  • Journal Article

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