Functional variants in the sucrase-isomaltase gene associate with increased risk of irritable bowel syndrome

Research output: Contribution to journalArticle


Objective IBS is a common gut disorder of uncertain pathogenesis. Among other factors, genetics and certain foods are proposed to contribute. Congenital sucrase- isomaltase deficiency (CSID) is a rare genetic form of disaccharide malabsorption characterised by diarrhoea, abdominal pain and bloating, which are features common to IBS. We tested sucrase-isomaltase (SI) gene variants for their potential relevance in IBS. Design We sequenced SI exons in seven familial cases, and screened four CSID mutations (p. Val557Gly, p. Gly1073Asp, p. Arg1124Ter and p. Phe1745Cys) and a common SI coding polymorphism (p. Val15Phe) in a multicentre cohort of 1887 cases and controls. We studied the effect of the 15Val to 15Phe substitution on SI function in vitro. We analysed p. Val15Phe genotype in relation to IBS status, stool frequency and faecal microbiota composition in 250 individuals from the general population. Results CSID mutations were more common in patients than asymptomatic controls (p=0.074; OR=1.84) and Exome Aggregation Consortium reference sequenced individuals (p=0.020; OR=1.57). 15Phe was detected in 6/7 sequenced familial cases, and increased IBS risk in case-control and population-based cohorts, with best evidence for diarrhoea phenotypes (combined p=0.00012; OR=1.36). In the population-based sample, 15Phe allele dosage correlated with stool frequency (p=0.026) and Parabacteroides faecal microbiota abundance (p=0.0024). The SI protein with 15Phe exhibited 35% reduced enzymatic activity in vitro compared with 15Val (p<0.05). Conclusions SI gene variants coding for disaccharidases with defective or reduced enzymatic activity predispose to IBS. This may help the identification of individuals at risk, and contribute to personalising treatment options in a subset of patients.


  • Maria Henström
  • Lena Diekmann
  • Ferdinando Bonfiglio
  • Fatemeh Hadizadeh
  • Eva Maria Kuech
  • Maren von Köckritz-Blickwede
  • Louise B. Thingholm
  • Tenghao Zheng
  • Ghazaleh Assadi
  • Claudia Dierks
  • Martin Heine
  • Ute Philipp
  • Ottmar Distl
  • Mary E. Money
  • Meriem Belheouane
  • Femke Anouska Heinsen
  • Joseph Rafter
  • Gerardo Nardone
  • Rosario Cuomo
  • Paolo Usai-Satta
  • Francesca Galeazzi
  • Matteo Neri
  • Susanna Walter
  • Magnus Simrén
  • Pontus Karling
  • Peter T. Schmidt
  • Greger Lindberg
  • Aldona Dlugosz
  • Lars Agreus
  • Anna Andreasson
  • Emeran Mayer
  • John F. Baines
  • Lars Engstrand
  • Piero Portincasa
  • Massimo Bellini
  • Vincenzo Stanghellini
  • Giovanni Barbara
  • Lin Chang
  • Michael Camilleri
  • Andre Franke
  • Hassan Y. Naim
  • Mauro D'Amato
External organisations
  • Karolinska Institutet
  • University of Veterinary Medicine Hannover
  • University of Kiel
  • Meritus Medical Center
  • University of Naples Federico II
  • Azienda Ospedaliera Brotzu
  • University Hospital of Padua
  • University of Chieti-Pescara
  • Linköping University
  • University of North Carolina
  • Umeå University
  • Karolinska University Hospital
  • Stressforskningsinstitutet, Stockholms universitet
  • Jonsson Comprehensive Cancer Center
  • University of Bari Aldo Moro
  • University of Pisa
  • St. Orsola-Malpighi University Hospital
  • Mayo Clinic Minnesota
  • Skåne University Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Genetics
  • Gastroenterology and Hepatology
Original languageEnglish
Pages (from-to)263-270
Issue number2
Early online date2016 Nov 21
Publication statusPublished - 2018
Publication categoryResearch