OBJECTIVE: To investigate linkage of candidate disease susceptibility genes to rheumatoid arthritis (RA) in affected sibling pair families stratified for specific clinical features. METHOD: Two hundred RA affected sibling pair families were genotyped for informative microsatellite markers mapping within or less than 3cM from: INF alpha, INF gamma, INF beta, IL1 alpha, IL1 beta, IL1R, IL2, IL6, IL5R, IL8R, BCL2, CD40L, NOS3, NRAMP, alpha 1 anti-trypsin, and alpha 1 anti-chymotrypsin, using fluorescence based automated technology. Linkage was examined by defining allele sharing sibling pairs. This was assessed by maximum likelihood-inheritance by descent methods. RESULTS: An increase in allele sharing was seen for IL5R in female sibling pairs (LOD 0.91, p = 0.03), for INF gamma 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). CONCLUSION: Weak evidence of linkage of RA to IL5R, IFN gamma, and IL2 has been detected in clinical subsets of sibling pairs suggesting that RA is a genetically heterogeneous disease.
OBJECTIVE: To investigate linkage of candidate disease susceptibility genes to rheumatoid arthritis (RA) in affected sibling pair families stratified for specific clinical features. METHOD: Two hundred RA affected sibling pair families were genotyped for informative microsatellite markers mapping within or less than 3cM from: INF alpha, INF gamma, INF beta, IL1 alpha, IL1 beta, IL1R, IL2, IL6, IL5R, IL8R, BCL2, CD40L, NOS3, NRAMP, alpha 1 anti-trypsin, and alpha 1 anti-chymotrypsin, using fluorescence based automated technology. Linkage was examined by defining allele sharing sibling pairs. This was assessed by maximum likelihood-inheritance by descent methods. RESULTS: An increase in allele sharing was seen for IL5R in female sibling pairs (LOD 0.91, p = 0.03), for INF gamma 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). CONCLUSION: Weak evidence of linkage of RA to IL5R, IFN gamma, and IL2 has been detected in clinical subsets of sibling pairs suggesting that RA is a genetically heterogeneous disease.
Authors: G Gyapay; J Morissette; A Vignal; C Dib; C Fizames; P Millasseau; S Marc; G Bernardi; M Lathrop; J Weissenbach Journal: Nat Genet Date: 1994-06 Impact factor: 38.330
Authors: J Worthington; W E Ollier; M K Leach; I Smith; E M Hay; W Thomson; L Pepper; D Carthy; A Farhan; S Martin Journal: Br J Rheumatol Date: 1994-10
Authors: C A McKenzie; C Julier; T Forrester; N McFarlane-Anderson; B Keavney; G M Lathrop; P J Ratcliffe; M Farrall Journal: Am J Hum Genet Date: 1995-12 Impact factor: 11.025
Authors: J B Copeman; F Cucca; C M Hearne; R J Cornall; P W Reed; K S Rønningen; D E Undlien; L Nisticò; R Buzzetti; R Tosi Journal: Nat Genet Date: 1995-01 Impact factor: 38.330
Authors: Andrzej Pawlik; Joanna Wrzesniewska; Marcin Florczak; Barbara Gawronska-Szklarz; Magdalena Herczynska Journal: Rheumatol Int Date: 2005-01-20 Impact factor: 2.631
Authors: Irit Chermesh; Aviva Azriel; Michal Alter-Koltunoff; Rami Eliakim; Amir Karban; Ben Zion Levi Journal: Dig Dis Sci Date: 2007-03-24 Impact factor: 3.487