SNFGE SNFGE
 
Thématique :
- Colo-proctologie
Originalité :
Très original
Solidité :
A confirmer
Doit faire évoluer notre pratique :
Pas encore
 
 
Nom du veilleur :
Professeur Frank ZERBIB
Coup de coeur :
 
 
Gut
  2018/02  
 
  2018 Feb;67(2):263-270.  
  doi: 10.1136/gutjnl-2016-312456  
 
  Functional variants in the sucrase-isomaltase gene associate with increased risk of irritable bowel syndrome.  
 
  Henström M, Diekmann L, Bonfiglio F, Hadizadeh F, Kuech EM, von Köckritz-Blickwede M, Thingholm LB, Zheng T, Assadi G, Dierks C, Heine M, Philipp U, Distl O, Money ME, Belheouane M, Heinsen FA, Rafter J, Nardone G, Cuomo R, Usai-Satta P, Galeazzi F, Neri M, Walter S, Simrén M, Karling P, Ohlsson B, Schmidt PT, Lindberg G, Dlugosz A, Agreus L, Andreasson A, Mayer E, Baines JF, Engstrand L, Portincasa P, Bellini M, Stanghellini V, Barbara G, Chang L, Camilleri M, Franke A, Naim HY, D'Amato M  
  https://www.ncbi.nlm.nih.gov/pubmed/27872184  
 
 

Abstract

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.

 

 
Question posée
 
Quelle est la fréquence des mutations du gène de la Sucrase isomaltase dans le SII ?
 
Question posée
 
Les hétérozygotes pour la mutation sont plus fréquents dans le SI que chez les témoins, particulièrement en cas de diarrhée.
 
Commentaires

L’idée d’anomalie génétique susceptible d’expliquer l’intolérance à certains sucres est intéressante. Mais sur 1300 patients testés, seuls 22 étaient mutés… et 10 témoins. C’est statistiquement significatif mais cliniquement peu pertinent. A suivre…

 
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