Genome wide scan in a Flemish inflammatory bowel disease population : support for the IBD4 locus, population heterogeneity, and epistasis

Vermeire, S.; Rutgeerts, P.; Van Steen, K.; Joossens, S.; Claessens, G.; Pierik, M.; Peeters, M.; Vlietinck, R.

doi:10.1136/GUT.2003.034033

Title

Genome wide scan in a Flemish inflammatory bowel disease population : support for the IBD4 locus, population heterogeneity, and epistasis

Author

Vermeire, S.

Rutgeerts, P.

Van Steen, K.

Joossens, S.

Claessens, G.

Pierik, M.

Peeters, M.

Vlietinck, R.

Abstract

Background and aims: Genome wide scans in inflammatory bowel disease (IBD) have indicated various susceptibility regions with replication of 16cen (IBD1), 12q (IBD2), 6p (IBD3), 14q11 (IBD4), and 3p21. As no linkage was previously found on IBD regions 3, 7, 12, and 16 in Flemish IBD families, a genome wide scan was performed to detect other susceptibility regions in this population. Methods: A cohort of 149 IBD affected relative pairs, all recruited from the Northern Flemish part of Belgium, were genotyped using microsatellite markers at 12 cM intervals, and analysed by Genehunter non-parametric linkage software. All families were further genotyped for the three main Crohns disease associated variants in the NOD2/CARD15 gene. Results: Nominal evidence for linkage was observed on chromosomes 1 (D1S197: multipoint non-parametric linkage (NPL) score 2.57, p = 0.004; and at D1S305-D1S252: NPL 2.97, p = 0.001), 4q (D4S406: NPL 1.95, p = 0.03), 6q16 (D6S314: NPL 2.44, p = 0.007), 10p12 (D10S197: NPL 2.05, p = 0.02), 11q22 (D11S35-D11S927: NPL 1.95, p = 0.02) 14q11-12 (D14S80: NPL 2.41, p = 0.008), 20p12 (D20S192: NPL 2.7, p = 0.003), and Xq (DXS990: NPL 1.70, p = 0.04). A total of 51.4% of patients carried at least one NOD2/CARD15 variant. Furthermore, epistasis was observed between susceptibility regions 6q/10p and 20p/10p. Conclusion: Genome scanning in a Flemish IBD population found nominal evidence for linkage on 1p, 4q, 10p12, and 14q11, overlapping with other genome scan results, with linkage on 14q11-12 supporting the IBD4 locus. The results further show that epistasis is contributing to the complex model of IBD and indicate that population heterogeneity is not to be underestimated. Finally, NOD2/CARD15 is clearly implicated in the Flemish IBD population.

Language

English

Source (journal)

Gut : the journal of the British Society for Gastroenterology / British Society for Gastroenterology. - London, 1960, currens

Publication

London : 2004

ISSN

0017-5749

DOI

10.1136/GUT.2003.034033

Volume/pages

53 :7 (2004) , p. 980-986