LINKAGE ANALYSIS OF CHROMOSOME 12 LOCI IN CROHN'S DISEASE FAMILIES.

Abstract

57 Background: Crohn's Disease is a multifactorial disease involving both genetic and environmental factors. A previous genome scan linkage analysis has localised a susceptibility locus for Inflammatory Bowel Diseases (IBD) on chromosome 12q21. This result was not uniformly confirmed in other populations. Aim: to determine if our set of European families may confirm the previously published linkage and linkage disequilibrium data on chromosome 12. Patients and methods: 58 multiplex families with several affected CD members were genotyped for 13 microsatellite markers evenly spread along the chromosome 12. Genotyping data were analyzed using a multipoint non parametric linkage analysis method (GENEHUNTER). Twenty five additional CD families were also genotyped for the D12S83 locus increasing the total number of affected sib-pairs to 80. At this locus, the identity by descent between affected sibs was determined and a transmission disequilibrium test was performed. Results: The 58 CD families did not exhibit evidence of linkage at any point of chromosome 12 (maximum non parametric lodscore = 0.21, p=0.4). At D12S83, corresponding to the maximum of the linkage tests in previously published data, the non parametric lodscore value was -0.36 (p=0.66). At this point, using the 80 affected sib-pairs, the mean of alleles shared was 0.48(X2 = 0.06, p=0,83) and the transmission disequilibrium test was not significant for any allele tested. Conclusion: These data do not confirm the previously reported linkage on chromosome 12 for Inflammatory Bowel Disease. This result may reflect genetic heterogeneity between European populations.