The NOD2-Smoking Interaction in Crohn's Disease is likely Specific to the 1007 fs 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, P. Lakatos, Paul L. Beck, Richard Fedorak, Levinus A. Dieleman, Karen Madsen, Remo Panaccione, Subrata Ghosh, Gilaad G. Kaplan

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 1007 fs variant across ages at diagnosis (≤ 16, 17–40, > 40 years). Findings Phase 1: Having ever smoked was less common among carriers of the 1007 fs 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 1007 fs variant decreased with age at diagnosis (≤ 16 years: 15%; 17–40: 12%; > 40: 3%; p = 0.003). Smoking was more common in older patients (≤ 16 years: 4%; 17–40: 48%; > 40: 71%; p < 0.001). Interpretation The negative NOD2-smoking interaction in Crohn's disease is specific to the 1007 fs 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
DOIs
Publication statusPublished - Jul 1 2017

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Crohn Disease
Meta-Analysis
Smoking
Mutation
Odds Ratio
Confidence Intervals
MEDLINE

Keywords

  • Age
  • Cigarette smoking
  • Crohn's disease
  • Gene-environment interactions
  • NOD2

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

The NOD2-Smoking Interaction in Crohn's Disease is likely Specific to the 1007 fs Mutation and may be Explained by Age at Diagnosis : A Meta-Analysis and Case-Only Study. / Kuenzig, M. Ellen; Yim, Jeff; Coward, Stephanie; Eksteen, Bertus; Seow, Cynthia H.; Barnabe, Cheryl; Barkema, Herman W.; Silverberg, Mark S.; Lakatos, P.; Beck, Paul L.; Fedorak, Richard; Dieleman, Levinus A.; Madsen, Karen; Panaccione, Remo; Ghosh, Subrata; Kaplan, Gilaad G.

In: EBioMedicine, Vol. 21, 01.07.2017, p. 188-196.

Research output: Contribution to journalArticle

Kuenzig, ME, Yim, J, Coward, S, Eksteen, B, Seow, CH, Barnabe, C, Barkema, HW, Silverberg, MS, Lakatos, P, Beck, PL, Fedorak, R, Dieleman, LA, Madsen, K, Panaccione, R, Ghosh, S & Kaplan, GG 2017, 'The NOD2-Smoking Interaction in Crohn's Disease is likely Specific to the 1007 fs Mutation and may be Explained by Age at Diagnosis: A Meta-Analysis and Case-Only Study', EBioMedicine, vol. 21, pp. 188-196. https://doi.org/10.1016/j.ebiom.2017.06.012
Kuenzig, M. Ellen ; Yim, Jeff ; Coward, Stephanie ; Eksteen, Bertus ; Seow, Cynthia H. ; Barnabe, Cheryl ; Barkema, Herman W. ; Silverberg, Mark S. ; Lakatos, P. ; Beck, Paul L. ; Fedorak, Richard ; Dieleman, Levinus A. ; Madsen, Karen ; Panaccione, Remo ; Ghosh, Subrata ; Kaplan, Gilaad G. / The NOD2-Smoking Interaction in Crohn's Disease is likely Specific to the 1007 fs Mutation and may be Explained by Age at Diagnosis : A Meta-Analysis and Case-Only Study. In: EBioMedicine. 2017 ; Vol. 21. pp. 188-196.
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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 1007 fs variant across ages at diagnosis (≤ 16, 17–40, > 40 years). Findings Phase 1: Having ever smoked was less common among carriers of the 1007 fs 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 1007 fs variant decreased with age at diagnosis (≤ 16 years: 15{\%}; 17–40: 12{\%}; > 40: 3{\%}; p = 0.003). Smoking was more common in older patients (≤ 16 years: 4{\%}; 17–40: 48{\%}; > 40: 71{\%}; p < 0.001). Interpretation The negative NOD2-smoking interaction in Crohn's disease is specific to the 1007 fs variant. However, opposing rates of this variant and smoking across age at diagnosis may explain this negative interaction.",
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T2 - A Meta-Analysis and Case-Only Study

AU - Kuenzig, M. Ellen

AU - Yim, Jeff

AU - Coward, Stephanie

AU - Eksteen, Bertus

AU - Seow, Cynthia H.

AU - Barnabe, Cheryl

AU - Barkema, Herman W.

AU - Silverberg, Mark S.

AU - Lakatos, P.

AU - Beck, Paul L.

AU - Fedorak, Richard

AU - Dieleman, Levinus A.

AU - Madsen, Karen

AU - Panaccione, Remo

AU - Ghosh, Subrata

AU - Kaplan, Gilaad G.

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N2 - 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 1007 fs variant across ages at diagnosis (≤ 16, 17–40, > 40 years). Findings Phase 1: Having ever smoked was less common among carriers of the 1007 fs 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 1007 fs variant decreased with age at diagnosis (≤ 16 years: 15%; 17–40: 12%; > 40: 3%; p = 0.003). Smoking was more common in older patients (≤ 16 years: 4%; 17–40: 48%; > 40: 71%; p < 0.001). Interpretation The negative NOD2-smoking interaction in Crohn's disease is specific to the 1007 fs variant. However, opposing rates of this variant and smoking across age at diagnosis may explain this negative interaction.

AB - 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 1007 fs variant across ages at diagnosis (≤ 16, 17–40, > 40 years). Findings Phase 1: Having ever smoked was less common among carriers of the 1007 fs 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 1007 fs variant decreased with age at diagnosis (≤ 16 years: 15%; 17–40: 12%; > 40: 3%; p = 0.003). Smoking was more common in older patients (≤ 16 years: 4%; 17–40: 48%; > 40: 71%; p < 0.001). Interpretation The negative NOD2-smoking interaction in Crohn's disease is specific to the 1007 fs variant. However, opposing rates of this variant and smoking across age at diagnosis may explain this negative interaction.

KW - Age

KW - Cigarette smoking

KW - Crohn's disease

KW - Gene-environment interactions

KW - NOD2

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