P236 - MEFV mutations modify the disease severity of inflammatory bowel disease

Abstract

binding protein 1, ABP1; EC 1.4.3.6). ABP1 enzyme activity in bowel mucosa of patients with IBD is 50% lower than in healthy individuals. The reason for this decrease remains unknown, but it may be due in part to polymorphisms in the ABP1 gene. The present study investigated whether a common single nucleotide polymorphism (SNP, refSNP ID: rs1049793), which is located in exon 3 C2029G) and cause amino acid substitutions (His645Asp) in the ABP1 enzyme, is related to CD. Aims: To analyse the association between the presence of a non-synonymous single nucleotide polymorphism at diamine oxidase gene and the risk of developing Crohn’s disease (CD) and to analyse its influence on the clinical course of these patients. Methods: In this prospective, case-control study, 210 unrelated Caucasian consecutive CD patients were recruited at the Inflammatory Bowel Disease Unit of a single tertiary centre (Hospital Clinico San Carlos) in Madrid, Spain. All patients were phenotyped and followed up for a median time of 8.7 years (range 4.1 14.5 years). A total of 261 healthy volunteers from the same geographic area were also recruited and matched with patients. Both cases and controls were analysed for the presence of His645Asp amino acid substitutions in the diamine oxidase enzyme, using amplification-restriction procedures. The protocol was approved by the Ethics Committee of the Hospital and all patients and controls gave informed consent before inclusion in the study. Results: No significant differences were found in the distribution of ABP1 alleles between CD patients and healthy volunteers [for variant alleles = OR 1.15 (95%CI 0.86 1.55)]. The distribution of ABP1 genotypes did not differ when patients were subdivided according to gender, mean age at diagnosis, mean duration of the disease, family history of IBD, smoking habit, previous appendectomy or tonsillectomy, Montreal classification, perianal CD, extraintestinal manifestations of CD (cutaneous, articular, ocular and hepatic) and severity, i.e. need for immunosuppressive therapies, biological treatments and/or surgery. Conclusion: Our results suggest that the His645Asp polymorphism of the histamine metabolising enzyme ABP1 may not be related to the risk of developing CD. Moreover, this gene does not seem to play a role in disease activity.