Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/57251
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Type: Journal article
Title: Collagen type III alpha 1 is a gastro-oesophageal reflux disease susceptibility gene and a male risk factor for hiatus hernia
Author: Asling, B.
Jirholt, J.
Hammond, P.
Knutsson, M.
Walentinsson, A.
Davidson, G.
Agreus, L.
Lehmann, A.
Lagerstrom-Fermer, M.
Citation: Gut, 2009; 58(8):1063-1069
Publisher: British Med Journal Publ Group
Issue Date: 2009
ISSN: 0017-5749
Statement of
Responsibility: 
B Åsling, J Jirholt, P Hammond, M Knutsson, A Walentinsson, G Davidson, L Agreus, A Lehmann, M Lagerström-Fermer
Abstract: Background and objectives: Gastro-oesophageal reflux disease (GORD) is a common gastrointestinal disorder with a genetic component. Our aim was to identify genetic factors associated with GORD. Patients and methods: Four separate patient cohorts were analysed using a step-wise approach. (1) Whole genome linkage analysis was performed in 36 families. (2) Candidate genes were tested for GORD association in a trio cohort. (3) Genetic association was replicated in a case–control cohort. We also investigated genetic association to hiatus hernia (HH). (4) Protein expression was analysed in oesophageal biopsies. Results: A region on chromosome 2, containing collagen type III alpha 1 (COL3A1), was identified (LOD = 3.3) in families with dominant transmission of GORD, stratified for hiatus hernia (HH). COL3A1 showed significant association with GORD in an independent paediatric trio cohort (pcorr = 0.003). The association was male specific (pcorr = 0.018). The COL3A1 association was replicated in an independent adult case control cohort (pcorr = 0.022). Moreover, male specific association to HH (pcorr = 0.019) was found for a SNP not associated to GORD. Collagen type III protein was more abundant in oesophageal biopsies from male patients with GORD (p = 0.03). Conclusion: COL3A1 is a disease-associated gene in both paediatric and adult GORD. Furthermore, we show that COL3A1 is genetically associated with HH in adult males. The GORD- and HH-associated alleles are different, indicating two separate mechanisms leading to disease. Our data provides new insight into GORD aetiology, identifying a connective tissue component and indicating a tissue remodelling mechanism in GORD. Our results implicate gender differences in the genetic risk for both for GORD and HH.
Description: Published Online First 26 April 2009
Rights: Copyright © 2009 BMJ Publishing Group Ltd & British Society of Gastroenterology.
RMID: 0020091114
DOI: 10.1136/gut.2008.167353
Appears in Collections:Paediatrics publications

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