Rare Hypomorphic Sucrase Isomaltase Variants in Relation to Irritable Bowel Syndrome Risk in UK Biobank

T. Zheng, L. Camargo-Tavares, F. Bonfiglio, F. Z. Marques, H. Y. Naim, M. D'amato

Research output: Contribution to journalShort SurveyOtherpeer-review

10 Citations (Scopus)


Sucrase-isomaltase (encoded by the SI gene) is the major intestinal brush border enzyme primarily responsible for the digestion of starch and sucrose.1 As seen in patients with congenital SI deficiency (a rare form of sucrose intolerance due to recessive mutations in the SI gene), inactive SI leads to colonic accumulation of unabsorbed carbohydrates, causing osmotic diarrhea, abdominal pain, and bloating.2,3 These symptoms are also typical of irritable bowel syndrome (IBS), and we recently reported (1) increased prevalence of rare (and the common Val15Phe) hypomorphic (defective) SI variants in patients with IBS, and (2) that IBS carriers of such variants are less likely to benefit from a low–fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) diet, which does not restrict sucrose and starch.4, 5, 6, 7 Preliminary evidence for the interaction between SI genotype, gut microbiota, and dietary carbohydrate intake in relation to IBS risk was also reported.5 Although this suggests carbohydrate malabsorption may contribute to IBS symptoms in some patients, these studies only tested known SI variants in up to 2200 IBS cases from tertiary centers (compared with publicly available data from ethnically matched populations), and the relevance of rare SI hypomorphic variants (hereafter referred to as rare pathogenic variants [RPVs]) toward IBS risk has not been investigated in large-scale studies at the general population level.
Original languageEnglish
Number of pages3
Issue number5
Publication statusPublished - 1 Nov 2021

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