title: Combined carriership of TLR9-1237C and CD14-260T alleles enhances the risk of developing chronic relapsing pouchitis.
abstract: OBJECTIVE
  To investigate the single nucleotide polymorphisms (SNPs) in genes involved in bacterial recognition and the susceptibility to pouchitis or pouchitis severity.
  
  
  METHODS
  Analyses of CD14 -260C>T, CARD15/NOD2 3020insC, Toll-like receptor (TLR)4 +896A>G, TLR9 -1237T>C, TLR9+2848G>A, and IRAKM + 22148G>A SNPs were performed in 157 ileal-pouch anal anastomosis (IPAA) patients (79 patients who did not develop pouchitis, 43 infrequent pouchitis patients, 35 chronic relapsing pouchitis patients) and 224 Italian Caucasian healthy controls.
  
  
  RESULTS
  No significant differences were found in SNP frequencies between controls and IPAA patients. However, a significant difference in carriership frequency of the TLR9-1237C allele was found between the infrequent pouchitis and chronic relapsing pouchitis groups [P = 0.028, oddos ratio (OR) = 3.2, 95%CI = 1.2-8.6]. This allele uniquely represented a 4-locus TLR9 haplotype comprising both studied TLR9 SNPs in Caucasians. Carrier trait analysis revealed an enhanced combined carriership of the alleles TLR9 -1237C and CD14 -260T in the chronic relapsing pouchitis and infrequent pouchitis group (P = 0.018, OR = 4.1, 95%CI = 1.4 -12.3).
  
  
  CONCLUSIONS
  There is no evidence that the SNPs predispose to the need for IPAA surgery. The significant increase of the combined carriership of the CD14 -260T and TLR9 -1237C alleles in the chronic relapsing pouchitis group suggests that these markers identify a subgroup of IPAA patients with a risk of developing chronic or refractory pouchitis.
authors.affiliation: Department Internal Medicine and Gastroenterology, Policlinic S. Orsola, University of Bologna, Nuove patologie-Pad. 5, Via Massarenti 9, 40138 Bologna, Italy. kmlammers@hotmail.com
authors.forename: K M
authors.initials: KM
authors.lastname: Lammers
authors.forename: S
authors.initials: S
authors.lastname: Ouburg
authors.forename: S A
authors.initials: SA
authors.lastname: Morré
authors.forename: J B A
authors.initials: JB
authors.lastname: Crusius
authors.forename: P
authors.initials: P
authors.lastname: Gionchett
authors.forename: F
authors.initials: F
authors.lastname: Rizzello
authors.forename: C
authors.initials: C
authors.lastname: Morselli
authors.forename: E
authors.initials: E
authors.lastname: Caramelli
authors.forename: R
authors.initials: R
authors.lastname: Conte
authors.forename: G
authors.initials: G
authors.lastname: Poggioli
authors.forename: M
authors.initials: M
authors.lastname: Campieri
authors.forename: A S
authors.initials: AS
authors.lastname: Peña
mesh_terms: D000328:Adult; D000483:Alleles; D001483:Base Sequence; D016022:Case-Control Studies; D002908:Chronic Disease; D039021:Colonic Pouches / Q000009:adverse effects; D004247:DNA / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D019449:Pouchitis / Q000209:etiology / Q000235:genetics* / Q000276:immunology*; D012008:Recurrence; D012307:Risk Factors; D051217:Toll-Like Receptor 9 / Q000235:genetics*
chemical_list: D018950:Lipopolysaccharide Receptors; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D004247:DNA