TITLE

INNATE IMMUNOGENETICS AND INFLAMMATORY BOWEL DISEASE (IBD)

AUTHOR(S)
McGovern, D.P.B.; van Heel, D.A.; Negoro, K.; Ahmad, T.; Jewell, D.P.
PUB. DATE
April 2003
SOURCE
Gut;Apr2003 Supplement 1, Vol. 52, pA59
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: The identification of NOD2(CARD15) as a susceptibility gene for Crohn's disease (CD) confirms the role of innate immunity in IBD. More recently a haplotype at IBD5 (Ch 5) has shown association with CD. Aims: To identify and test innate immunity single nucleotide polymorphisms (SNPs) for association with IBD. Methods: Interesting (positional and functional) SNPs were identified from databases or by direct sequencing. A two-stage approach was adopted to overcome problems of multiple testing. Stage 1: Casecontrol analysis (191 CD, 247 ulcerative colitis (UC) and 240 controls (HC)). Stage 2: Positive results from stage 1 to be confirmed by the transmission-disequilibrium test (TDT) (556 IBD (294 CD and 252 UC) trios). AIl results were stratified by phenotype and NOD2/IBD5 geno. Results: Case-control analysis (all % allele frequency (p value)): Toll-like receptor (TLR) 2, 3 intronic SNPs and 1 microsatellite marker, no IBD association. TLR2 'bacterial hyporesponsive' SNP (R753Q), HC 4.0, IBD 2.5 (0.13), UC 2.4 (0.12) and CD 2.6 (0.25). Fulminant UC requiring surgery (130 cases) 4.3%, 'mild' UC not requiring surgery (135 cases) 0.4% (0.0032)(OR 0.08). TLR4 SNP (bronchial hypo-responsiveness) HC 4.4, CD 3.1 (0.34) and UC (4.9 (0.71). Two novel MAL (TIRAP) SNPs, 4 novel Triggering receptor expressed on myeloid cells -1 (TREM-1) SNPs, TLR9 SNP, 4 P2X7 SNPs, and lactoferrin SNP, all-no association seen with any IBD geno- or phenotype. TDT analysis (transmissions/non-transmissions): TLR4 SNP (A896G): IBD 64/44 (0.054), UC 11/11, CD 36/23 (0.098), CD NOD2 negative 28/18 (0.14). Conclusions: These innate immunity SNPs are not significantly associated with IBD. The colectomy, non-colectomy TLR2 association suggests that intact innate immunity is needed for the development of fulminant UC. Studies of other SNPs in the innate immune system and their role in IBD are warranted.
ACCESSION #
9747681

 

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