title: Association between tumor necrosis factor receptor II and familial, but not sporadic, rheumatoid arthritis: evidence for genetic heterogeneity.
abstract: OBJECTIVE
  Tumor necrosis factor alpha (TNFalpha) binds the receptors TNFRI and TNFRII. Results of genome scans have suggested that TNFR2 is a candidate rheumatoid arthritis (RA) locus. A case-control study in a UK Caucasian population has shown an association between a TNFR2 genotype (196R/R in exon 6) and familial, but not sporadic, RA. The present study was undertaken to test this association in the French Caucasian population.
  
  
  METHODS
  To test for an association in sporadic RA, 100 families were genotyped for the 196M/R polymorphism and analyzed using the transmission disequilibrium test and haplotype relative risk. To test for an association in familial RA, RA index cases from 100 affected sibpair (ASP) families were genotyped for 196M/R. Linkage analysis was performed with 3 TNFR2 microsatellite markers.
  
  
  RESULTS
  The TNFR2 196R/R genotype was not associated with sporadic RA (odds ratio [OR] 0.59, P = 0.72), but was associated with familial RA (OR 4.0, P = 0.026). The association was most marked in the context of TNFR2 "twin-like" RA sibs (affected sibs sharing both TNFR2 haplotypes) (OR 9.2, P = 0.0017). Linkage analysis results were consistent with the association; most of the TNFR2 linkage evidence was found in the subgroup of families with 196R/R ASP index cases.
  
  
  CONCLUSIONS
  This study is the first to replicate evidence of the involvement of TNFR2 in RA genetic heterogeneity. Our data refine the initial hypothesis, to suggest that a TNFR2 recessive factor, in linkage disequilibrium with the 196R allele, plays a major role in a subset of families with multiple cases of RA.
authors.affiliation: GenHotel, Evry-Genopole, France. dieude@polyarthrite.net
authors.forename: Philippe
authors.initials: P
authors.lastname: Dieudé
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Petit
authors.forename: Séverine
authors.initials: S
authors.lastname: Cailleau-Moindrault
authors.forename: José
authors.initials: J
authors.lastname: Osorio
authors.forename: Céline
authors.initials: C
authors.lastname: Pierlot
authors.forename: Maria
authors.initials: M
authors.lastname: Martinez
authors.forename: Sabine
authors.initials: S
authors.lastname: Fauré
authors.forename: Olivier
authors.initials: O
authors.lastname: Alibert
authors.forename: Sandra
authors.initials: S
authors.lastname: Lasbleiz
authors.forename: Claudia
authors.initials: C
authors.lastname: De Toma
authors.forename: Thomas
authors.initials: T
authors.lastname: Bardin
authors.forename: Bernard
authors.initials: B
authors.lastname: Prum
authors.forename: François
authors.initials: F
authors.lastname: Cornélis
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000032:analysis; D005260:Female; D018740:Genetic Heterogeneity; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D018895:Microsatellite Repeats; D011110:Polymorphism, Genetic; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics* / Q000378:metabolism; D047889:Receptors, Tumor Necrosis Factor, Type II
chemical_list: D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047889:Receptors, Tumor Necrosis Factor, Type II; D004247:DNA