Linkage of rheumatoid arthritis to the candidate gene NRAMP1 on 2q35.
The macrophage resistance gene NRAMP1 regulates priming/activation of macrophages for enhanced TNF alpha, IL 1 beta, and MHC class II expression. Since all of these functions are of potential importance in the induction or maintenance or both of autoimmune disease, samples from the Arthritis and Rheumatism Council's repository of multicase rheumatoid arthritis families were typed for a dinucleotide repeat in the NRAMP1 promoter region and four other 2q34 (TNP1) or 2q35 (IL8R, VIL1, DES) marker genes. Identity by descent (IBD) sib pair analysis using a three locus haplotype NRAMP1-IL8RB-VIL1, or NRAMP1 alone, provided preliminary evidence (maximum lod score = 1.01, p = 0.024) for a gene in this region contributing to suceptibility to rheumatoid arthritis. Candidacy for NRAMP1 as the disease susceptibility gene was supported by a significant bias (p = 0.048) towards transmission of the NRAMP1 promoter region allele 3 in affected offspring.
Shaw
M A
MA
Department of Medicine, University of Cambridge Clinical School, Addenbrooke's Hospital, UK.
Clayton
D
D
Atkinson
S E
SE
Williams
H
H
Miller
N
N
Sibthorpe
D
D
Blackwell
J M
JM
D001172:Arthritis, Rheumatoid / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D027682:Cation Transport Proteins; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D018900:Dinucleotide Repeats / Q000235:genetics; D005796:Genes / Q000235:genetics; D008040:Genetic Linkage; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D016013:Likelihood Functions; D008565:Membrane Proteins / Q000235:genetics*; D009679:Nuclear Family; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011401:Promoter Regions, Genetic / Q000235:genetics; D000099173:Natural Resistance-associated Macrophage Protein 1
D002352:Carrier Proteins; D027682:Cation Transport Proteins; D005819:Genetic Markers; D008565:Membrane Proteins; D000099173:Natural Resistance-associated Macrophage Protein 1