MUTATION SCREENING IN THE CD19 AND CD43 (SIALOPHORIN) GENES IN CROHN DISEASE PATIENTS

Abstract

57 Background: A susceptibility locus for Crohn Disease (CD) has been mapped on chromosome 16. CD19 and CD43 genes are located in the genetic region of interest. They encode for membrane receptors of the lymphocyte. CD19 is involved in the B lymphocyte response and CD43 is a ligand for the ICAM1 gene which has been reported to be associated with Inflammatory Bowel Diseases. Thus they appear as good candidate genes for CD. Aim of the study : To detect polymorphism's within the coding sequence of these genes. In case of a sequence variation with a functional effect, to test for a transmission disequilibrium between the polymorphism and the disease. Patients and methods : DNA's from 10 unrelated CD patients and 2 healthy controls have been sequenced for the full coding sequence of the 2 genes, including the intron-exon junctions. For the non silent mutation of CD19 exon 3, a transmission disequilibrium was searched using the TDT in 78 CD families (TDT-like from the Analyse package). Results : Two sequence variations were found within the exon 2 of the CD43 gene. However, these polymorphism's do not change the protein sequence (silent mutations). Two other polymorphism's were identified within the exons 3 and 4 of the CD19 gene. The former is a missense mutation (G2481C) changing the amino acid sequence (valin → leucin). The later is a silent mutation. No transmission disequilibrium was observed for the missense mutation. Conclusion : This study demonstrates that several polymorphism's are present within the coding sequences of the CD19 and CD43 genes. However, for most of them, their functional consequences are expected to be limited. For the missense mutation of the CD19 exon 3, the absence of transmission disequilibrium with the disease demonstrates that it is not associated with the disease. Taken together, these findings suggest that the CD19 and CD43 genes are not involved in the genetic predisposition to CD in this family set.

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