Functional Variation in Human CAZyme Genes in Relation to the Efficacy of a Carbohydrate-Restricted Diet in IBS Patients

Zamfir-Taranu, Andreea; Löscher, Britt-Sabina; Carbone, Florencia; Hoter, Abdullah; Esteban Blanco, Cristina; Bozzarelli, Isotta; Torices, Leire; Routhiaux, Karen; Van den Houte, Karen; Bonfiglio, Ferdinando; Mayr, Gabriele; Corsetti, Maura; Naim, Hassan Y.; Franke, Andre; Tack, Jan; D’Amato, Mauro

Abstract

Background & Aims
Limiting the dietary intake of certain carbohydrates has therapeutic effects in some but not all irritable bowel syndrome (IBS) patients. We investigated genetic variation in human Carbohydrate-Active enZYmes (hCAZymes) genes in relationship to the response to a FODMAP-lowering diet in the DOMINO study.
Methods
hCAZy polymorphism was studied in patients with IBS from the dietary (FODMAP-lowering; n = 196) and medication (otilonium bromide; n = 54) arms of the DOMINO trial via targeted sequencing of 6 genes of interest (AMY2B, LCT, MGAM, MGAM2, SI, and TREH). hCAZyme defective (hypomorphic) variants were identified via computational annotation using clinical pathogenicity classifiers. Age- and sex-adjusted logistic regression was used to test hCAZyme polymorphisms in cumulative analyses where IBS patients were stratified into carrier and non-carrier groups (collapsing all hCAZyme hypomorphic variants into a single bin). Quantitative analysis of hCAZyme variation was also performed, in which the number of hCAZyme genes affected by a hypomorphic variant was taken into account.
Results
In the dietary arm, the number of hypomorphic hCAZyme genes positively correlated with treatment response rate (P = .03; odds ratio = 1.51; confidence interval = 0.99–2.32). In the IBS-D group (n = 55), hCAZyme carriers were 6 times more likely to respond to the diet than non-carriers (P = .002; odds ratio = 6.33; confidence interval = 1.83–24.77). These trends were not observed in the medication arm.
Conclusions
hCAZYme genetic variation may be relevant to the efficacy of a carbohydrate-lowering diet. This warrants additional testing and replication of findings, including mechanistic investigations of this phenomenon.

Citation

Zamfir-Taranu, A., Löscher, B.-S., Carbone, F., Hoter, A., Esteban Blanco, C., Bozzarelli, I., Torices, L., Routhiaux, K., Van den Houte, K., Bonfiglio, F., Mayr, G., Corsetti, M., Naim, H. Y., Franke, A., Tack, J., & D’Amato, M. (2024). Functional Variation in Human CAZyme Genes in Relation to the Efficacy of a Carbohydrate-Restricted Diet in IBS Patients. Clinical Gastroenterology and Hepatology, https://doi.org/10.1016/j.cgh.2024.09.004

• Journal Article Type: Article
• Acceptance Date: Sep 23, 2024
• Online Publication Date: Oct 14, 2024
• Publication Date: Oct 14, 2024
• Deposit Date: Oct 25, 2024
• Publicly Available Date: Oct 31, 2024
• Journal: Clinical Gastroenterology and Hepatology
• Print ISSN: 1542-3565
• Electronic ISSN: 1542-7714
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.1016/j.cgh.2024.09.004
• Public URL: https://nottingham-repository.worktribe.com/output/40870602
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S154235652400870X