2008 Barcelona - European Society of Human Genetics

Molecular and biochemical basis of disease
Dis . 2008 Feb; 67(2):248-50 . Epub 2007 Jul 2 .) . The aim of this study
was to investigate the statistical interaction of this CD susceptibility
factor and rs2241880 (A1338G, T300A) of the autophagy-related 16like
1 (ATG16L1) gene (Hampe et al .; Nat Genet . 2007; 39:207) . 198
Hungarian patients with CD and 225 healthy controls were genotyped
by PCR-RFLP methods. We found significantly higher frequency for
the ATG16L1 G allele and GG genotype in the CD cohort compared
to controls (p=0 .008, OR=1 .454, 95% CI: 1 .106-1 .910; p=0 .0001,
OR=3 .460, 95% CI: 2 .086-5 .740) . The frequencies and odds ratios of
rs10889677 genotypes were stratified by rs2241880 genotypes. The
ATG16L1 AG genotype significantly increased the risk for CD on the
background of IL23R 3’-UTR CA and AA (p CA =0 .043, OR=2 .522, 95%
CI: 1 .043-6 .097; p AA =0 .013, OR=4 .550, 95% CI: 1 .464-14 .145) . The
ATG16L1 GG genotype significantly increased the risk for CD with the
susceptibility alleles of IL23R 3’-UTR (p CA =0 .004, OR=4 .000, 95% CI:
1 .553-10 .306; p AA =0 .0001, OR=32 .50, 95% CI: 3 .59-294 .216) . The
significantly highest relative odds ratios for rs2241880 were detected
on the background of the IL23R AA genotype, suggesting the risk alleles
of these two disease-associated loci have an additive effect .
P06.070
IL RL -IL R -IL RAP-SLC A and CARD loci are
susceptibility factors for both crohn’s disease and ulcerative
colitis
E. A. M. Festen 1 , A. Zhernakova 2 , L. Franke 2 , G. Trynka 1 , C. C. van Diemen 1 ,
M. Bevova 2 , R. M. Nijmeijer 2 , R. Heijmans 3 , H. M. Boezen 1 , D. A. Van Heel 4 ,
A. A. van Bodegraven 3 , P. C. F. Stokkers 5 , C. Wijmenga 1 , B. A. Crusius 3 , R. K.
Weersma 1 ;
1 University Medical Centre Groningen, Groningen, The Netherlands, 2 University
Medical Centre Utrecht, Utrecht, The Netherlands, 3 VU Medical Centre, Amsterdam,
The Netherlands, 4 Queen Mary’s School of Medicine and Dentistry,
London, United Kingdom, 5 Academic Medical Center, Amsterdam, The Netherlands.
The two main phenotypes of inflammatory bowel disease (IBD) -
Crohn’s disease (CD) and ulcerative colitis (UC) - are chronic intestinal
inflammatory disorders with a complex genetic background.
We performed a functional candidate gene analysis within the innate
immune pathway in IBD using a three-stage design . In phase I, 354
SNPs from 85 innate immunity genes were typed in a cohort of 520
Dutch IBD patients (284 CD, 236 UC) and 808 controls . In phase II, 9
SNPs showing association at p