Potential association between irritable bowel syndrome and the gene encoding human intestinal sucrase-isomaltase (LB131)

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder characterized by abdominal pain and alterations in bowel pattern with a prevalence of 10-15 % in humans. The molecular basis of IBS is not well understood. We sequenced the coding region of the sucrase-isomaltase gene (SI) in a mother and her two children who suffer from IBS. The only polymorphism we found to be homozygous or heterozygous was Val15Phe (V15F, rs9290264, g.7526G>T, c.43G>T). We assessed the role of this exchange at the biochemical, cellular and functional levels by expressing SI containing V15F (SI-V15F) in COS-1 cells. The biosynthesis, glycosylation and folding of SI-V15F were essentially comparable to those in wild type SI. The substitution of Val in the first α-helix of the transmembrane domain of SI by a bulky Phe may have implications on the mode of association of SI with the inner leaflet of the membrane. For this, we investigated the association of SI-V15F with lipid rafts by assessment of its solubility...