Extended reports
Linkage of cytokine genes to rheumatoid arthritis. Evidence of
genetic heterogeneity
Arthritis
and Rheumatism Council's Epidemiology Research Unit, University of
Manchester, Manchester
Correspondence to: Dr S John, ARC Epidemiology Research Unit, University of Manchester, Stopford Building, Oxford Road, Manchester M13 9PT.
Accepted for publication 7 April 1998
OBJECTIVE
To investigate linkage of candidate
disease susceptibility genes to rheumatoid arthritis (RA) in affected
sibling pair families stratified for specific clinical features.
METHODTwo hundred RA affected sibling pair
families were genotyped for informative microsatellite markers mapping
within or less than 3cM from: INF
, INF
, INF
, IL1, IL1,
IL1R, IL2, IL6, IL5R, IL8R, BCL2, CD40L, NOS3, NRAMP, 1
anti-trypsin, and 1 anti-chymotrypsin, using
fluorescence based automated technology. Linkage was examined by
defining allele sharing sibling pairs. This was assessed by maximum
likelihoodinheritance by descent methods.
RESULTSAn increase in allele sharing was seen for
IL5R in female sibling pairs (LOD 0.91, p = 0.03), for INF in
sibling pairs with an affected male (LOD 0.96, p = 0.03) and most
significantly for IL2 in sibling pairs where one or both were
persistently seronegative (LOD 1.05, p = 0.02).
CONCLUSIONWeak evidence of linkage of RA to IL5R,
IFN, and IL2 has been detected in clinical subsets of sibling pairs
suggesting that RA is a genetically heterogeneous disease.
© 1998 by Annals of the Rheumatic Diseases
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