Irritable bowel syndrome is a common gut disorder of uncertain pathogenesis.
Among other factors, genetics and certain foods are proposed to contribute.
Congenital sucrase–isomaltase deficiency is a rare genetic form of disaccharide malabsorption characterized by diarrhea, abdominal pain and bloating, which are features common to irritable bowel syndrome.
Dr Mauro D'Amato and colleagues from Sweden tested sucrase–isomaltase gene variants for their potential relevance in irritable bowel syndrome.
The team sequenced sucrase–isomaltase exons in 7 familial cases, and screened 4 congenital sucrase–isomaltase deficiency mutations, and a common sucrase–isomaltase coding polymorphism in a multicenter cohort of 1887 cases and controls.
The researchers studied the effect of the 15Val to 15Phe substitution on sucrase–isomaltase function in vitro.
|The sucrase–isomaltase protein with 15Phe exhibited 35% reduced enzymatic activity in vitro compared with 15Val|
The doctors analyzed p.Val15Phe genotype in relation to irritable bowel syndrome status, stool frequency and fecal microbiota composition in 250 individuals from the general population.
The team found that congenital sucrase–isomaltase deficiency mutations were more common in patients than asymptomatic controls and Exome Aggregation Consortium reference sequenced individuals.
15Phe was detected in 6/7 sequenced familial cases, and increased irritable bowel syndrome risk in case–control and population-based cohorts, with best evidence for diarrhea phenotypes.
In the population-based sample, 15Phe allele dosage correlated with stool frequency and parabacteroides fecal microbiota abundance.
The sucrase–isomaltase protein with 15Phe exhibited 35% reduced enzymatic activity in vitro compared with 15Val.
Dr D'Amato's team concludes, "Sucrase–isomaltase gene variants coding for disaccharidases with defective or reduced enzymatic activity predispose to irritable bowel syndrome."
"This may help the identification of individuals at risk."