Analysis of the CARD15 variants R702W, G908R and L1007fs in Italian IBD patients.

CARD15 on chromosome 16 is the only IBD susceptibility gene identified among several mapped loci. Its recurrent variants R702W, G908R and L1007fs have shown significant association with Crohn's disease (CD), but not with ulcerative colitis (UC), in different Caucasian populations. We analysed these three variants in 184 CD and 92 UC Italian patients and in 177 healthy controls. L1007fs and G908R were independently associated with CD, while R702W showed a nonsignificant increase. After combining the three variants together, 32.6% of CD patients were positive vs 18.6% of the controls. The association was stronger for homozygotes and compound heterozygotes, OR 13.9 (1.8-108), and weaker but still significant for simple heterozygotes, OR 1.7 (1.0-2.9). An excess of homozygotes/compound heterozygotes also resulted from the comparison with Hardy-Weinberg expectations. Phenotype-genotype correlations were analysed first by univariate logistic regression and then by multivariate analysis, the effect of CARD15 positivity being adjusted according to the status of smoking, familiarity and sex, so as to focus on the predictivity of genetic and environmental risk factors on the clinical phenotype. Significant risk estimates of the CARD15 genotype were obtained for stricturing vs inflammatory behaviour, OR 2.76 (1.2-6.3), and for penetrating behaviour, 2.59 (1.0-6.6), and marginally significant for ileal vs colic location, OR 3.0 (0.9-9.8). Our findings indicate that the association of the CARD15 genotype with behaviour and location of disease holds also for the Italian population.

Red cell distribution width as a marker of coeliac disease: a prospective study.

BACKGROUND: Coeliac disease is frequently underdiagnosed because of its protean presentations. Serological tests may be helpful in screening programmes for populations at risk, but they are costly. AIM: To determine prospectively whether a commonly available haematological test such as the red cell distribution width (RDW) could be of help in detecting unrecognized coeliac disease. METHODS: Of 353 consecutive adult patients referred to our outpatient malabsorption clinic, 198 in whom clinical suspicion was strong were referred for further investigations and intestinal biopsy. Seventy-six inflammatory bowel disease outpatients and 90 subjects admitted for diseases other than malabsorption were enrolled as the control group. RESULTS: RDW was increased in 94 (47.4%) and normal in 104 (52.5%) of 198 patients. Duodenal biopsy confirmed coeliac disease in 80 (85.1%) of the former patients and 69 (66.3%) of the latter patients. No correlation between RDW values and histological scores was found. Overall RDW increase was found in 80/149 (53.7%) patients with a definite diagnosis of coeliac disease, and in 14/49 (28.6%) patients in whom biopsy excluded the disease. A 1-year gluten withdrawal led to a significant decrease in RDW value, even in patients with obdurate mucosal impairment. CONCLUSIONS: In patients in whom there is a strong clinical suspicion of coeliac disease, an elevated RDW despite normal haemoglobin concentration may be a reliable predictor of the disease.