• sucrase-isomaltase gene variants
• irritable bowel syndrome
• intestinal function
• protein trafficking
• enzyme function
• low FODMAP diet

Recent seminal reports in GUT 1 2 have proposed an association between gene variants of intestinal sucrase-isomaltase (SI) and the onset of irritable bowel syndrome (IBS).3 An increased risk of IBS-D (diarrhoea) symptoms in individuals harbouring the variant Val15Phe in the SI gene has been proposed due to partial trafficking impairment and reduced overall function of SI at the cell surface.1 2 These observations strongly suggested an association between Val15Phe and the onset of typical IBS-D symptoms (eg, diarrhoea and bloating4), which are similar to those in congenital SI deficiency.5 The presence of other SI gene variants (SIGVs) has been associated with poorer symptom response to a low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet in IBS-D.2 However, molecular, cellular and functional analyses of these variants are required to explain their potential effects on the digestive function of SI and diminished efficacy of the low FODMAP diet in reducing symptoms in patients with these variants. We therefore generated mutants of SI that harbour these SIGVs, namely R774G [rs147207752], Y975H [rs146785675] and E1414K [rs145734588]), by site-directed mutagenesis, expressed them in …