title: [Polymorphism of the microsatellites and tumor necrosis factor genes in chronic inflammatory bowel diseases].
abstract: OBJECTIVE
  Multiplex family studies have excluded chromosome 6 as a candidate gene of susceptibility to inflammatory bowel disease. However, one recent study suggested that a gene involved in the pathogenesis of Crohn's disease is located on chromosome 6 confering to a microsatellite allelic combination (a2, b1, c2, d4, e1) a strong genetic risk factor in Crohn's disease. The aim of our study was to determine simultaneously the polymorphisms of the TNF microsatellites and of the genes coding for TNF synthesis in patients with inflammatory bowel disease.
  
  
  METHODS
  Sixty patients with ulcerative colitis, 100 patients with Crohn's disease were compared to 64 healthy ethnically 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 length polymorphism (RFLP).
  
  
  RESULTS
  Allelic frequencies of TNF microsatellites and of TNF alpha and beta genes were similar in Crohn's disease, ulcerative colitis and controls. Five loci microsatellite haplotypes, especially a2 b1 c2 d4 e1 allelic combination, were not more frequent in Crohn's disease (25%) compared to ulcerative colitis (27%) or controls (20%). Subgroups stratification according to clinical characteristics did not modify haplotype frequencies. Analysis of our data taking simultaneously into account the MHC alleles (DRB*01 or DRB1*04) did not modify our data; however, it suggested that extended haplotype on short arm of chromosome 6 differed between patients and controls. Linkage disequilibrium (delta = -360.10(-4); P < 0.01) between a2, b1, c2, d4, e1 allelic combination and DRB1*04 allele was observed only in Crohn's disease.
  
  
  CONCLUSIONS
  Percentages of patients with Crohn's disease or ulcerative colitis carrying TNF microsatellite or TNF alpha and beta gene haplotypes were similar to those of healthy controls. These data argue against involvement of the TNF locus without exclusion of short arm of chromosome 6 implication in Crohn's disease pathogenesis.
authors.affiliation: Service d'Hépato-Gastro-Entérologie, C.H.R.U. Pontchaillou, Rennes.
authors.forename: D
authors.initials: D
authors.lastname: Heresbach
authors.forename: A
authors.initials: A
authors.lastname: Ababou
authors.forename: A
authors.initials: A
authors.lastname: Bourienne
authors.forename: M
authors.initials: M
authors.lastname: Alizadeh
authors.forename: E
authors.initials: E
authors.lastname: Quelvennec
authors.forename: M
authors.initials: M
authors.lastname: Pagenault
authors.forename: A
authors.initials: A
authors.lastname: Dabadie
authors.forename: N H
authors.initials: NH
authors.lastname: Berre
authors.forename: J P
authors.initials: JP
authors.lastname: Campion
authors.forename: B
authors.initials: B
authors.lastname: Launois
authors.forename: M
authors.initials: M
authors.lastname: Gosselin
authors.forename: B
authors.initials: B
authors.lastname: Genetet
authors.forename: J F
authors.initials: JF
authors.lastname: Bretagne
authors.forename: G
authors.initials: G
authors.lastname: Semana
mesh_terms: D000328:Adult; D000483:Alleles; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6; D002908:Chronic Disease; D003093:Colitis, Ulcerative / Q000235:genetics; D003424:Crohn Disease / Q000235:genetics; D004198:Disease Susceptibility; D005260:Female; D006239:Haplotypes; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D011110:Polymorphism, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D014409:Tumor Necrosis Factor-alpha
vernacular_title: Etude du polymorphisme des microsatellites et des gènes du tumor necrosis factor (TNF) au cours des maladies inflammatoires chroniques de l'intestin.