Genetic Variation in the Familial Mediterranean Fever Gene (MEFV) and Risk for Crohn's Disease and Ulcerative Colitis

BACKGROUND AND AIMS: The familial Mediterranean fever (FMF) gene (MEFV) encodes pyrin, a major regulator of the inflammasome platform controlling caspase-1 activation and IL-1beta processing. Pyrin has been shown to interact with the gene product of NLRP3, NALP3/cryopyrin, also an important active member of the inflammasome. The NLRP3 region was recently reported to be associated with Crohn's disease (CD) susceptibility. We therefore sought to evaluate MEFV as an inflammatory bowel disease (IBD) susceptibility gene. METHODOLOGY AND RESULTS: MEFV colonic mucosal gene expression was significantly increased in experimental colitis mice models (TNBS p<0.0003; DSS p<0.006), in biopsies from CD (p<0.02) and severe ulcerative colitis (UC) patients (p<0.008). Comprehensive genetic screening of the MEFV region in the Belgian exploratory sample set (440 CD trios, 137 UC trios, 239 CD cases, 96 UC cases, and 107 healthy controls) identified SNPs located in the MEFV 5' haplotype block that were significantly associated with UC (rs224217; p = 0.003; A allele frequency: 56% cases, 45% controls), while no CD associations were observed. Sequencing and subsequent genotyping of variants located in this associated haplotype block identified three synonymous variants (D102D/rs224225, G138G/rs224224, A165A/rs224223) and one non-synonymous variant (R202Q/rs224222) located in MEFV exon 2 that were significantly associated with UC (rs224222: p = 0.0005; A allele frequency: 32% in cases, 23% in controls). No consistent associations were observed in additional Canadian (256 CD trios, 91 UC trios) and Scottish (495 UC, 370 controls) sample sets. We note that rs224222 showed marginal association (p = 0.012; G allele frequency: 82% in cases, 70% in controls) in the Canadian sample, but with a different risk allele. None of the NLRP3 common variants were associated with UC in the Belgian-Canadian UC samples and no significant interactions were observed between NLRP3 and MEFV that could explain the observed flip-flop of the rs224222 risk allele. CONCLUSION: The differences in association levels observed between the sample sets may be a consequence of distinct founder effects or of the relative small sample size of the cohorts evaluated in this study. However, the results suggest that common variants in the MEFV region do not contribute to CD and UC susceptibility.Journal ArticleResearch Support, N.I.H. ExtramuralResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

The preference for an endoscopist specific sex: a link between ethnic origin, religious belief, socioeconomic status, and procedure type

Adi Lahat,1 Yehudith Assouline-Dayan,1 Lior H Katz,1 Herma H Fidder2 1Chaim Sheba Medical Center, Tel Hashomer, Israel; 2Department of Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, The Netherlands Background and aim: The sex of the physician performing the endoscopic procedure is one of the parameters influencing patient satisfaction. Our aim was to characterize patients&rsquo; preferences according to their sex, socioeconomic status, and religious beliefs and according to procedure-related variables. Methods: All patients undergoing an endoscopic procedure at Sheba Hospital between April 2012 and September 2012 were asked to complete a questionnaire regarding their sex, ethnic background, socioeconomic status, religious practice, and preference for an endoscopist of a specific sex. Questionnaires were included for analysis only when more than 95% of the items were addressed. Results: A total of 1,009 patients agreed to complete the questionnaires; of these 946 (94% [59% male]) were eligible for inclusion. Most patients (675 [70%]) expressed no preference for sex of the endoscopist, while 234 patients (25%) preferred a same-sex endoscopist, and only 55 (6%) preferred an other-sex endoscopist. Stepwise logistic regression analysis showed that in female patients, lower education (odds ratio [OR] = 1.28), non-Jewish religion (OR = 4.86), orthodox religious practice (OR = 2.28), African or Asian ethnic origin (OR = 2.44), scheduled for colonoscopy (OR = 1.90), and no previous endoscopy experience (OR = 1.88) were all associated with a preference for a same-sex endoscopist. Conclusion: One-quarter of patients preferred the physician performing their examination to be of particular sex. Most of these patients preferred a same-sex endoscopist. Education level, intensity of religious practice, ethnic origin, and type of endoscopic examination were associated with a preference for a same-sex endoscopist. Addressing patients&rsquo; preferences may improve the atmosphere in the clinical environment, reduce stress, and facilitate better treatment and adherence to endoscopic surveillance programs. Keywords: endoscopy, patients&rsquo; satisfaction, compliance, patient&rsquo;s preferenc

Budesonide foam vs. hydrocortisone acetate foam in the treatment of active ulcerative proctosigmoiditis

INTRODUCI'ION: Rectal administration of corticosteroids is advocated in patients with proctosigmoiditis who have failed therapy with mesalamine enema. Foam offers patients better tolerability than an enema. In this study the efficacy and adverse effects of a new budesonide foam are compared with the presently available hydrocortisone foam. METHODS: Two hundred fifty-one patients with proctosigmoiditis were randomly assigned to receive either budesonide foam or hydrocortisone foam for eight weeks. RESULTS: Remission rates were comparable in the budesonide and hydrocortisone groups, 53 and 52 percent, respectively. The mean disease activity index for the two groups decreased to a similar extent, from 7.2 +/- 1.9 and 7 +/- 2 to 3.6 +/- 3.1 and 3.9 +/- 3.4 in the budesonide and hydrocortisone groups, respectively. In a subgroup of patients who had not responded to rectal administration of mesalamine, 23 of 44 (52 percent) patients who received budesonide responded favorably to the foam, as compared with 14 of 38 (37 percent) patients who received hydrocortisone (P = not significant). Low plasma cortisol occurred in 3 percent of the budesonide group and in none of the hydrocortisone patients. CONCLUSIONS: This trial demonstrates a similar efficacy and safety of the two foams in patients with proctosigmoiditis