title: The telomeric part of the HLA region predisposes to rheumatoid arthritis independently of the class II loci.
abstract: We have evaluated the possible contribution of genes besides DQ and DR to the association of HLA with rheumatoid arthritis (RA). To this end, we have looked at the allele distributions of six microsatellites, D6S1014, D6S2673, TNFalpha, MIB, C1-2-5, and C1-3-2 among 132 RA patients and 254 controls. We have defined 19 microsatellite clusters corresponding to previously described ancestral haplotypes. One of them was D6S1014*143-D6S273*139-TNFalpha*99-MIB*350-C1-2-5*196-C1-3-2*354, often found associated with DQB1*0201-DRB1*0301. As part of this microsatellite cluster, the allele MIB*350 was found to be a RA-predisposing factor, independent of DRB1*0301 and RA-predisposing haplotypes DQB1*03-DRB1*04 and DQB1*0501-DRB1*01. We conclude that the telomeric part of the HLA region contains a locus conferring predisposition to RA independently of HLA class II.
authors.affiliation: Department of Immunohaematology and Blood Transfusion, Leiden University Medical Centre, The Netherlands. e.h.zanelli@lumc.nl
authors.forename: E
authors.initials: E
authors.lastname: Zanelli
authors.forename: G
authors.initials: G
authors.lastname: Jones
authors.forename: M
authors.initials: M
authors.lastname: Pascual
authors.forename: P
authors.initials: P
authors.lastname: Eerligh
authors.forename: A R
authors.initials: AR
authors.lastname: van der Slik
authors.forename: A H
authors.initials: AH
authors.lastname: Zwinderman
authors.forename: W
authors.initials: W
authors.lastname: Verduyn
authors.forename: G M
authors.initials: GM
authors.lastname: Schreuder
authors.forename: E
authors.initials: E
authors.lastname: Roovers
authors.forename: F C
authors.initials: FC
authors.lastname: Breedveld
authors.forename: R R
authors.initials: RR
authors.lastname: de Vries
authors.forename: J
authors.initials: J
authors.lastname: Martin
authors.forename: M J
authors.initials: MJ
authors.lastname: Giphart
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology*; D005802:Genes, MHC Class II; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006680:HLA Antigens / Q000235:genetics*; D006681:HLA-D Antigens / Q000235:genetics; D006801:Humans; D018895:Microsatellite Repeats / Q000235:genetics / Q000276:immunology; D016615:Telomere / Q000235:genetics* / Q000276:immunology*
chemical_list: D006680:HLA Antigens; D006681:HLA-D Antigens