TUMOR-NECROSIS-FACTOR GENE AND MICROSATEL LITE POLYMORPHISM IN CHRONIC INFLAMMATORY BOWEL DISEASES

Objectives. - Multiplex family studies have excluded chromosome 6 as a candidate gene of susceptibility to inflammatory bowel disease. Howev er one recent study suggested that a gene involved in the pathogenesis of Crohn's disease is located on chromosome 6 confering to a microsat ellite allelic combination (a2, b1, c2, d4, e1) a strong genetic risk factor in Crohn's disease. The aim of our study was to determine simul taneously the polymorphisms of the TNF microsatellites and of the the genes coding for TNF synthesis in patients with inflammatory bowel dis ease. Patients and methods. - Sixty patients with ulcerative colitis, 100 patients with Crohn's disease were compared to 64 healthy ethnical ly matched controls. Five TNF microsatellite loci (a, b, c, d, e) were typed using polymerase chain reaction PCR, and two dimorphisms of TNF alpha and TNF beta (intron 1) were studied by restriction fragment le ngth polymorphism (RFLP). Results. - Allelic frequencies of TNF micros atellites and of TNF alpha and beta genes were similar in Crohn's dise ase, ulcerative colitis and controls. Five loci microsatellite haploty pes, especially a2 b1 c2 d4 e1 allelic combination, were not more freq uent in Crohn's disease (25 %) compared to ulcerative colitis (27 %) o r controls (20 %). Subgroups stratification according to clinical char acteristics did not modify haplotype frequencies. Analysis of our data taking simultaneously into account the MHC alleles (DRB101 or DRB1*0 4) did not modify our data ; however it suggested that extended haplot ype on short arm of chromosome 6 differed between patients and control s. Linkage disequilibrium (Delta = -360.10(-4); P < 0.01) between a2, b1, c2, d4, e1 allelic combination and DRB104 allele was observed onl y in Crohn's disease. Conclusion. - Percentages of patients with Crohn 's disease or ulcerative colitis carrying TNF microsatellite or TNF al pha and beta gene haplotypes were similar to those of healthy controls . These data argue against involvement of the TNF locus without exclus ion of short arm of chromosome 6 implication in Crohn's disease pathog enesis.