Title: New susceptibility locus for rheumatoid arthritis suggested by a genome-wide linkage study
Authors: Cornélis, F ×
Fauré, S
Martinez, M
Prud'homme, J F
Fritz, P
Dib, C
Alves, H
Barrera, P
de Vries, N
Balsa, A
Pascual-Salcedo, D
Maenaut, K
Westhovens, Rene
Migliorini, P
Tran, T H
Delaye, A
Prince, N
Lefevre, C
Thomas, G
Poirier, M
Soubigou, S
Alibert, O
Lasbleiz, S
Fouix, S
Bouchier, C
Lioté, F
Loste, M N
Lepage, V
Charron, D
Gyapay, G
Lopes-Vaz, A
Kuntz, D
Bardin, T
Weissenbach, J #
Issue Date: Sep-1998
Series Title: Proceedings of the National Academy of Sciences of the United States of America vol:95 issue:18 pages:10746-50
Abstract: Rheumatoid arthritis (RA), the most common autoimmune disease, is associated in families with other autoimmune diseases, including insulin-dependent diabetes mellitus (IDDM). Its genetic component has been suggested by familial aggregation (lambdas = 5), twin studies, and segregation analysis. HLA, which is the only susceptibility locus known, has been estimated to account for one-third of this component. The aim of this paper was to identify new RA loci. A genome scan was performed with 114 European Caucasian RA sib pairs from 97 nuclear families. Linkage was significant only for HLA (P < 2.5.10(-5)) and nominal for 19 markers in 14 other regions (P < 0.05). Four of the loci implicated in IDDM potentially overlap with these regions: the putative IDDM6, IDDM9, IDDM13, and DXS998 loci. The first two of these candidate regions, defined in the RA genome scan by the markers D18S68-D18S61-D18S469 (18q22-23) and D3S1267 (3q13), respectively, were studied in 194 additional RA sib pairs from 164 nuclear families. Support for linkage to chromosome 3 only was extended significantly (P = 0.002). The analysis of all 261 families provided a linkage evidence of P = 0. 001 and suggested an interaction between this putative RA locus and HLA. This locus could account for 16% of the genetic component of RA. Candidate genes include those coding for CD80 and CD86, molecules involved in antigen-specific T cell recognition. In conclusion, this first genome scan in RA Caucasian families revealed 14 candidate regions, one of which was supported further by the study of a second set of families.
ISSN: 0027-8424
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Rheumatology Section (-)
× corresponding author
# (joint) last author

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