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

Henström, M., Diekmann, L., Bonfiglio, F., Hadizadeh, F., Kuech, E.-M., von Köckritz-Blickwede, M., et al. (2016). Functional variants in the sucrase–isomaltase gene associate with increased risk of irritable bowel syndrome. Gut. doi:10.1136/gutjnl-2016-312456.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002C-0C48-0 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002C-0C49-E
Genre: Journal Article

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 Creators:
Henström, Maria, Author
Diekmann, Lena, Author
Bonfiglio, Ferdinando, Author
Hadizadeh, Fatemeh, Author
Kuech, Eva-Maria, Author
von Köckritz-Blickwede, Maren, Author
Thingholm, Louise B, Author
Zheng, Tenghao, Author
Assadi, Ghazaleh, Author
Dierks, Claudia, Author
Heine, Martin, Author
Philipp, Ute, Author
Distl, Ottmar, Author
Money, Mary E, Author
Belheouane, Meriem1, Author              
Heinsen, Femke-Anouska, Author
Rafter, Joseph, Author
Nardone, Gerardo, Author
Cuomo, Rosario, Author
Usai-Satta, Paolo, Author
Galeazzi, Francesca, AuthorNeri, Matteo, AuthorWalter, Susanna, AuthorSimrén, Magnus, AuthorKarling, Pontus, AuthorOhlsson, Bodil, AuthorSchmidt, Peter T, AuthorLindberg, Greger, AuthorDlugosz, Aldona, AuthorAgreus, Lars, AuthorAndreasson, Anna, AuthorMayer, Emeran, AuthorBaines, John F.1, Author              Engstrand, Lars, AuthorPortincasa, Piero, AuthorBellini, Massimo, AuthorStanghellini, Vincenzo, AuthorBarbara, Giovanni, AuthorChang, Lin, AuthorCamilleri, Michael, AuthorFranke, Andre, AuthorNaim, Hassan Y, AuthorD'Amato, Mauro, Author more..
Affiliations:
1Guest Group Evolutionary Genomics, Max Planck Institute for Evolutionary Biology, Max Planck Society, ou_1445638              

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 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.

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Language(s): eng - English
 Dates: 2016-06-162016-10-312016-10-312016-11
 Publication Status: Published in print
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 Rev. Method: Peer
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Title: Gut
  Other : Gut
Source Genre: Journal
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Publ. Info: London : British Medical Association
Pages: - Volume / Issue: - Sequence Number: - Start / End Page: - Identifier: ISSN: 0017-5749
CoNE: /journals/resource/954925402606

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Title: Gut
  Other : Gut
Source Genre: Journal
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Publ. Info: London : BMJ Publishing Group
Pages: 8 Seiten Volume / Issue: 0 Sequence Number: - Start / End Page: - Identifier: Other: 1468-3288
ISSN: 0017-5749
CoNE: /journals/resource/954925402606