An analysis of phenotype - genotype features of a maltese patient cohort with crohn's disease and ulcerative colitis

Abstract

Crohn's disease (CD) and Ulcerative colitis (UC) are the two major fonns of inflammato1y bowel diseases (IBD) with a multifactorial aetiology. Genetic studies have identified 163 susceptibility loci for IBD, mostly shared between CD and UC. We undertook a study in our local IBD population. The aims of our study were: • To determine if the phenotype of the Maltese IBD patients is similar to that of the European cohorts. • To determine the frequency of the NOD2/CARD 15 polymorphisms (Arg702Trp, Gly908Arg and Leu1007insC mutations) in our CD patients as compared to the European Population. • To detennine if the genetic architecture of the Maltese population is similar to the European population. • To determine if the prevalence of common IBD polymorphisms (rs35261698, rs2172252, rs3197999, rs4151651, rs3129891, rs9268832, rs482044, rs2066844, rs2066847, rs6887695, rs4833095, rs187238, rs1004819, rs11209026 and rs2241880) are present in the Maltese IBD patients when compared to a Maltese Control population. • To determine if there is any correlation between the phenotype and the genotypes of both patients with UC and CD. Methods: Patients with IBD who fulfilled the Copenhagen criteria (Langholz, 1999) for its diagnosis were recruited from Mater Dei Hospital, Malta. The patients' clinical case notes were reviewed and the patients were interviewed. Informed consent was obtained. Their phenotypic and clinical features were entered into a database. Blood was withdrawn from the patients. A control group was recruited. DNA extraction was then done at the Department of Physiology, University of Malta. Analysis for the NOD2/CARD 15 polymorphisms was done at the University of Malta. Further analysis on the extracted DNA samples was done at the University of Kiel, Germany. The extracted DNA was sent over and the genetic analysis was done using the Immunochip version 2. Results: 194 patients with CD, 109 patients with UC and 216 healthy volunteer controls, age and gender matched were randomly recruited. Their phenotypic features were similar to that described in other European populations. Analysis of the DNA in CD patients for the NOD2/CARD 15 polymorphisms revealed a mutation rate of 12%, which is statistically much lower than that found in European Populations (p= <0.005). The genetic architecture of the Maltese population is similar to that of the European population, especially of those people from Tuscany, Italy. Data from the Immunochip v2 was compared using a Manhattan plot. This demonstrated the absence of statistically significant SNPs in our IBD population when compared to the European IBD population. [...]