Innate immune receptor genetic polymorphisms in pouchitis: is CARD15 a susceptibility factor?
BACKGROUND
Pouchitis is a frequent complication after ileal pouch-anal anastamosis (IPAA) for ulcerative colitis (UC). The aim of this study was to determine whether genetic polymorphisms in the innate immune receptors toll-like receptor (TLR)4 and caspase activation and recruitment domain family member 15 (CARD15) genes are associated with pouchitis.


METHODS
From a retrospectively ascertained cohort of patients with UC 5 to 12 years after IPAA (n = 101), subjects were classified into 3 groups: no pouchitis (n = 52); 1 to 2 episodes per year (n = 11), and more than 2 episodes per year (n = 38). Single nucleotide polymorphisms in the tlr4 gene (D299G, T399I) were determined by a real-time polymerase chain reaction-based fluorogenic probe technique; and card15 polymorphisms (L1007fsinsC, R702W, G908R) were determined by pyrosequencing.


RESULTS
Pouchitis affected 49% (49/101) of the study population. No correlation between pouchitis and the presence of TLR4 polymorphisms was found. The percentage of patients who harbored CARD15 mutations was significantly higher in patients with pouchitis than in patients without pouchitis (18% versus 8%; P < 0.05); 24% of pouchitis patients with more than 2 episodes per year harbored CARD15 mutations (P < 0.01 compared with the no pouchitis group). The CARD15 insertion mutation L1007fsinsC was present in 14% of patients with pouchitis and in 0% without pouchitis (P < 0.05). All patients who carried L1007fsinsC developed more than 2 episodes per year.


CONCLUSIONS
CARD15 polymorphisms are seen in greater frequency in patients with pouchitis after IPAA for UC. These findings, if borne out in prospective analyses, suggest that CARD15 mutations, particularly L1007fsinsC, may predispose to the development of pouchitis after IPAA for UC.
Meier
Carmen B
CB
Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
Hegazi
Refaat A
RA
Aisenberg
James
J
Legnani
Peter E
PE
Nilubol
Naris
N
Cobrin
Gena M
GM
Duerr
Richard H
RH
Gorfine
Stephen R
SR
Bauer
Joel J
JJ
Sachar
David B
DB
Plevy
Scott E
SE
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D003093:Colitis, Ulcerative / Q000601:surgery; D039021:Colonic Pouches; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein; D011110:Polymorphism, Genetic; D019449:Pouchitis / Q000235:genetics*; D012189:Retrospective Studies
D047908:Intracellular Signaling Peptides and Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein