ATG16L1 rs2241880/T300A increases susceptibility to perianal Crohn's disease: An updated meta-analysis on inflammatory bowel disease risk and clinical outcomes

Simovic, Isidora and Hilmi, Ida and Ng, Ruey Terng and Chew, Kee Seang and Wong, Shin Yee and Lee, Way Seah and Riordan, Stephen and Castano-Rodriguez, Natalia (2024) ATG16L1 rs2241880/T300A increases susceptibility to perianal Crohn's disease: An updated meta-analysis on inflammatory bowel disease risk and clinical outcomes. United European Gastroenterology Journal, 12 (1). pp. 103-121. ISSN 2050-6406, DOI https://doi.org/10.1002/ueg2.12477.

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Abstract

BackgroundATG16L1 plays a fundamental role in the degradative intracellular pathway known as autophagy, being a mediator of inflammation and microbial homeostasis. The variant rs2241880 can diminish these capabilities, potentially contributing to inflammatory bowel disease (IBD) pathogenesis.ObjectivesTo perform an updated meta-analysis on the association between ATG16L1 rs2241880 and IBD susceptibility by exploring the impact of age, ethnicity, and geography. Moreover, to investigate the association between rs2241880 and clinical features.MethodsLiterature searches up until September 2022 across 7 electronic public databases were performed for all case-control studies on ATG16L1 rs2241880 and IBD. Pooled odds ratios (ORP) and 95% CI were calculated under the random effects model.ResultsOur analyses included a total of 30,606 IBD patients, comprising 21,270 Crohn's disease (CD) and 9336 ulcerative colitis (UC) patients, and 33,329 controls. ATG16L1 rs2241880 was significantly associated with CD susceptibility, where the A allele was protective (ORP: 0.74, 95% CI: 0.72-0.77, p-value: <0.001), while the G allele was a risk factor (ORP: 1.23, 95% CI: 1.09-1.39, p-value: 0.001), depending on the minor allele frequencies observed in this multi-ancestry study sample. rs2241880 was predominantly relevant in Caucasians from North America and Europe, and in Latin American populations. Importantly, CD patients harbouring the G allele were significantly more predisposed to perianal disease (ORP: 1.21, 95% CI: 1.07-1.38, p-value: 0.003).ConclusionsATG16L1 rs2241880 (G allele) is a consistent risk factor for IBD in Caucasian cohorts and influences clinical outcomes. As its role in non-Caucasian populations remains ambiguous, further studies in under-reported populations are necessary. image

Item Type: Article
Funders: UNSPECIFIED
Uncontrolled Keywords: Autophagy; Biomarker; Crohn disease; IBD; Inflammatory bowel disease; Perianal; Risk factor; rs2241880; Ulcerative colitis
Subjects: R Medicine > R Medicine (General)
R Medicine > RJ Pediatrics
Divisions: Faculty of Medicine > Medicine Department
Faculty of Medicine > Paediatrics Department
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 06 Nov 2024 08:25
Last Modified: 06 Nov 2024 08:25
URI: http://eprints.um.edu.my/id/eprint/46002

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