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Dietary Iron and Heme Iron Consumption, Genetic Susceptibility, and Risk of Crohn's Disease and Ulcerative Colitis.
Inflamm Bowel Dis 2017; 23(7):1088-1095IB

Abstract

BACKGROUND

Dietary iron and heme, likely through their effect on gut commensal bacteria and colonic barrier function, have been shown to modulate colonic inflammation in animal models of colitis. Nonetheless, the link between dietary total and heme iron and risk of Crohn's disease (CD) and ulcerative colitis (UC) has not been previously explored.

METHODS

We conducted a prospective cohort study of 165,331 U.S. women enrolled in the Nurses' Health Study and Nurses' Health Study II. Dietary information was collected using a validated food frequency questionnaire at baseline (1984) and updated every 2 to 4 years. Self-reported CD and UC diagnoses were confirmed through medical records review. We used Cox proportional hazard models to calculate hazard ratios and 95% confidence intervals while adjusting for potential confounders. In a case-control study nested within these cohorts, we evaluated the interaction between single-nucleotide polymorphisms associated with genome-wide susceptibility to CD and UC and dietary total and heme iron intake on risk of CD and UC using logistic regression modeling.

RESULTS

Through 2011, over 3,038,049 person-years of follow-up, we documented 261 incident cases of CD and 321 incident cases of UC. Dietary heme iron was nonsignificantly associated with increased risk of UC (Ptrend = 0.12). This association seemed to be modified by the UC susceptibility locus, rs1801274, a coding variant in the FcγRIIA gene (Pinteraction = 7.00E-05). In contrast, there was no association between dietary heme iron and risk of CD (Ptrend = 0.67). We also did not observe an association between total dietary intake of iron and risk of CD or UC (All Ptrend > 0.35).

CONCLUSION

In 2 large prospective cohort studies, dietary total and heme iron were not associated with risk of CD or UC. Our suggestive finding that the association between dietary heme iron intake and risk of UC may be modified by a coding variant in FcγRIIA gene warrants additional investigation.

Authors+Show Affiliations

*Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; †Clinical and Translation Epidemiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; ‡Division of Gastroenterology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; §Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; and ‖The Broad Institute, Cambridge, Massachusetts.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28604414

Citation

Khalili, Hamed, et al. "Dietary Iron and Heme Iron Consumption, Genetic Susceptibility, and Risk of Crohn's Disease and Ulcerative Colitis." Inflammatory Bowel Diseases, vol. 23, no. 7, 2017, pp. 1088-1095.
Khalili H, de Silva PS, Ananthakrishnan AN, et al. Dietary Iron and Heme Iron Consumption, Genetic Susceptibility, and Risk of Crohn's Disease and Ulcerative Colitis. Inflamm Bowel Dis. 2017;23(7):1088-1095.
Khalili, H., de Silva, P. S., Ananthakrishnan, A. N., Lochhead, P., Joshi, A., Garber, J. J., ... Chan, A. T. (2017). Dietary Iron and Heme Iron Consumption, Genetic Susceptibility, and Risk of Crohn's Disease and Ulcerative Colitis. Inflammatory Bowel Diseases, 23(7), pp. 1088-1095. doi:10.1097/MIB.0000000000001161.
Khalili H, et al. Dietary Iron and Heme Iron Consumption, Genetic Susceptibility, and Risk of Crohn's Disease and Ulcerative Colitis. Inflamm Bowel Dis. 2017;23(7):1088-1095. PubMed PMID: 28604414.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dietary Iron and Heme Iron Consumption, Genetic Susceptibility, and Risk of Crohn's Disease and Ulcerative Colitis. AU - Khalili,Hamed, AU - de Silva,Punyanganie S, AU - Ananthakrishnan,Ashwin N, AU - Lochhead,Paul, AU - Joshi,Amit, AU - Garber,John J, AU - Richter,James R, AU - Sauk,Jenny, AU - Chan,Andrew T, PY - 2017/6/13/pubmed PY - 2018/4/25/medline PY - 2017/6/13/entrez SP - 1088 EP - 1095 JF - Inflammatory bowel diseases JO - Inflamm. Bowel Dis. VL - 23 IS - 7 N2 - BACKGROUND: Dietary iron and heme, likely through their effect on gut commensal bacteria and colonic barrier function, have been shown to modulate colonic inflammation in animal models of colitis. Nonetheless, the link between dietary total and heme iron and risk of Crohn's disease (CD) and ulcerative colitis (UC) has not been previously explored. METHODS: We conducted a prospective cohort study of 165,331 U.S. women enrolled in the Nurses' Health Study and Nurses' Health Study II. Dietary information was collected using a validated food frequency questionnaire at baseline (1984) and updated every 2 to 4 years. Self-reported CD and UC diagnoses were confirmed through medical records review. We used Cox proportional hazard models to calculate hazard ratios and 95% confidence intervals while adjusting for potential confounders. In a case-control study nested within these cohorts, we evaluated the interaction between single-nucleotide polymorphisms associated with genome-wide susceptibility to CD and UC and dietary total and heme iron intake on risk of CD and UC using logistic regression modeling. RESULTS: Through 2011, over 3,038,049 person-years of follow-up, we documented 261 incident cases of CD and 321 incident cases of UC. Dietary heme iron was nonsignificantly associated with increased risk of UC (Ptrend = 0.12). This association seemed to be modified by the UC susceptibility locus, rs1801274, a coding variant in the FcγRIIA gene (Pinteraction = 7.00E-05). In contrast, there was no association between dietary heme iron and risk of CD (Ptrend = 0.67). We also did not observe an association between total dietary intake of iron and risk of CD or UC (All Ptrend > 0.35). CONCLUSION: In 2 large prospective cohort studies, dietary total and heme iron were not associated with risk of CD or UC. Our suggestive finding that the association between dietary heme iron intake and risk of UC may be modified by a coding variant in FcγRIIA gene warrants additional investigation. SN - 1536-4844 UR - https://www.unboundmedicine.com/medline/citation/28604414/Dietary_Iron_and_Heme_Iron_Consumption_Genetic_Susceptibility_and_Risk_of_Crohn's_Disease_and_Ulcerative_Colitis_ L2 - https://academic.oup.com/ibdjournal/article-lookup/doi/10.1097/MIB.0000000000001161 DB - PRIME DP - Unbound Medicine ER -