Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

CARD15/NOD2 Risk Alleles in the Development of Crohn's Disease in the Australian Population

CARD15/NOD2 Risk Alleles in the Development of Crohn's Disease in the Australian Population We have previously reported strong evidence for linkage between IBD1 and Crohn's disease (CD) in Australian Crohn's disease families. Three risk alleles for Crohn's disease, (Arg702Trp (C/T), Gly908Arg (G/C) and 980fs981 (‐/C), were recently identified in the CARD15/NOD2 gene on chromosome 16, implicating this as the IBD1 locus. Using a novel diagnostic PCR‐RFLP, we have examined the frequency of these alleles in 205 multiplex IBD families, 107 sporadic Crohn's disease cases and 409 normal individuals. We demonstrate that the three risk alleles are more frequent in Crohn's disease, than in controls, with allelic frequencies of 0.11, 0.02 and 0.07 respectively. Heterozygosity for individual variants conferred a three‐fold increase in risk for Crohn's disease while substantially higher risks were associated with being homozygous or compound heterozygous. Despite a significantly lower population allele frequency for the frameshift mutation than reported by other groups, we see a similar contribution by this allele to the risk of developing Crohn's disease. While the three risk alleles influence susceptibility to Crohn's disease in Australia, we show that these alleles do not fully explain the linkage evidence and suggest that there are very likely additional IBD1 susceptibility alleles yet to be described in Australian CD at the NOD2 locus. We also show a second linkage peak in Australian CD that provides some support for a second disease susceptibility locus on chromosome 16. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Annals of Human Genetics Wiley

CARD15/NOD2 Risk Alleles in the Development of Crohn's Disease in the Australian Population

Download PDF
7 pages

Loading next page...
 
/lp/wiley/card15-nod2-risk-alleles-in-the-development-of-crohn-s-disease-in-the-n0jCqbLjE7

References (21)

Publisher
Wiley
Copyright
Copyright © 2003 Wiley Subscription Services
ISSN
0003-4800
eISSN
1469-1809
DOI
10.1046/j.1469-1809.2003.00006.x
Publisher site
See Article on Publisher Site

Abstract

We have previously reported strong evidence for linkage between IBD1 and Crohn's disease (CD) in Australian Crohn's disease families. Three risk alleles for Crohn's disease, (Arg702Trp (C/T), Gly908Arg (G/C) and 980fs981 (‐/C), were recently identified in the CARD15/NOD2 gene on chromosome 16, implicating this as the IBD1 locus. Using a novel diagnostic PCR‐RFLP, we have examined the frequency of these alleles in 205 multiplex IBD families, 107 sporadic Crohn's disease cases and 409 normal individuals. We demonstrate that the three risk alleles are more frequent in Crohn's disease, than in controls, with allelic frequencies of 0.11, 0.02 and 0.07 respectively. Heterozygosity for individual variants conferred a three‐fold increase in risk for Crohn's disease while substantially higher risks were associated with being homozygous or compound heterozygous. Despite a significantly lower population allele frequency for the frameshift mutation than reported by other groups, we see a similar contribution by this allele to the risk of developing Crohn's disease. While the three risk alleles influence susceptibility to Crohn's disease in Australia, we show that these alleles do not fully explain the linkage evidence and suggest that there are very likely additional IBD1 susceptibility alleles yet to be described in Australian CD at the NOD2 locus. We also show a second linkage peak in Australian CD that provides some support for a second disease susceptibility locus on chromosome 16.

Journal

Annals of Human Genetics – Wiley

Published: Jan 1, 2003

There are no references for this article.