Genetic analyses of treatment response in primary care IBS, a pilot study

Balsiger, Lukas M.; Houte, Karen Van den; Zheng, Tenghao; Tóth, Joran; Besard, Linde; Franke, André; D’Amato, Mauro; Tack, Jan; Carbone, Florencia

doi:10.1136/gutjnl-2022-328430

Cited by 1 publication

(1 citation statement)

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“…ANNOVAR [32] was used for functional annotation of hCAZyme variants, in order to filter for coding missense (non-synonymous and/or stop-gain/loss) changes, before assigning pathogenicity scores (see below). GSA genotyping data available for DOMINO participants [33] was used for cohort-level quality controls, filtering our individuals of non-European ancestry, with missing data, heterozygosity rate >6SD and/or calling rate <0.85.…”

Section: Targeted Sequencing Of Hcazyme Genesmentioning

confidence: 99%

Functional variation in human Carbohydrate-Active enZYmes (hCAZymes) in relation to the efficacy of a FODMAP-reducing diet in IBS patients

Zamfir-Taranu,

Löscher,

Carbone

et al. 2024

Preprint

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Objective: Limiting the dietary intake of carbohydrates poorly absorbed in the small intestine (FODMAPs) 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 relation to the response to a FODMAP-lowering diet in the DOMINO study. Design: hCAZy polymorphism was studied in IBS patients 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=0.03, OR=1.51 [CI=0.99-2.32]). In the IBS-D group (N=55), hCAZyme carriers were six times more likely to respond to the diet than non-carriers (P=0.002, OR=6.33 [CI=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. Keywords: Irritable bowel syndrome; nutrigenetics; lowFODMAP diet; carbohydrate maldigestion; CAZyme

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Section: Targeted Sequencing Of Hcazyme Genesmentioning

confidence: 99%