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World J Gastroenterol. Dec 14, 2005; 11(46): 7323-7329
Published online Dec 14, 2005. doi: 10.3748/wjg.v11.i46.7323
Combined carriership of TLR9 -1237C and CD14 -260T alleles enhances the risk of developing chronic relapsing pouchitis
KM Lammers, S Ouburg, SA Morré, JBA Crusius, P Gionchetti, F Rizzello, C Morselli, E Caramelli, R Conte, G Poggioli, M Campieri, AS Peña
KM Lammers, P Gionchetti, F Rizzello, C Morselli, M Campieri, Department of Internal Medicine and Gastroenterology, Policlinico S. Orsola, University of Bologna, Bologna, Italy
S Ouburg, SA Morré, JBA Crusius, AS Peña, Laboratory of Immunogenetics, VU University Medical Center, Amsterdam, The Netherlands
E Caramelli, Institute of Histology and General Embryology, University of Bologna, Bologna, Italy
R Conte, Department of Immunohaematology and Blood Transfusion, Policlinico S. Orsola, University of Bologna, Bologna, Italy
AS Peña, Laboratory of Immunogenetics and Department of Gastroenterology, VU University Medical Center, Amsterdam, The Netherlands
G Poggioli, Department of Surgery and Organ Transplantation, Policlinic S. Orsola, University of Bologna, Bologna, Italy
Author contributions: All authors contributed equally to the work.
Correspondence to: KM Lammers, Department Internal Medicine and Gastroenterology, Policlinic S. Orsola, University of Bologna, Nuove patologie-Pad. 5, Via Massarenti 9, 40138 Bologna, Italy. kmlammers@hotmail.com
Telephone: +39-51-6364122 Fax: +39-51-392538
Received: May 2, 2005
Revised: June 2, 2005
Accepted: June 9, 2005
Published online: December 14, 2005
Abstract

AIM: 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, odd’s 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).

CONCLUSION: 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.

Keywords: Pouchitis; Innate immunity; Single nucleotide polymorphisms; CD14; TLR9