RESEARCH - A genome-wide scan for JRA in affected sibpair families provides evidence of linkage

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Arthritis Rheum. 2004 Sep;50(9):2920-30.

A genome-wide scan for juvenile rheumatoid arthritis in affected sibpair

families provides evidence of linkage.

SD, Moroldo MB, Guyer L, M, Tombragel EM, Shear ES,

Prahalad S, Sudman M, Keddache MA, Brown WM, Giannini EH, Langefeld CD,

Rich SS, Nichols WC, Glass DN.

Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229,

USA.

OBJECTIVE: Juvenile rheumatoid arthritis (JRA) represents a

heterogeneous group of disorders with a complex genetic component. A

genome scan was performed to detect linkage to JRA in 121 families

containing 247 affected children in North America (the JRA Affected

Sibpair [ASP] Registry). METHODS: Genotype data collected for HLA-DR and

386 microsatellite markers were subjected to multipoint nonparametric

linkage analysis. Following analysis of the entire set of families,

additional analyses were performed after a priori stratification by

disease onset type, age at onset, disease course, and selected HLA-DRB1

alleles. RESULTS: Linkage of JRA to the HLA region was confirmed

(logarithm of odds [LOD] score 2.26). Additional evidence supporting

linkage of JRA was observed at 1p36 (D1S214; LOD 1.65), 19p13 (D19S216;

LOD 1.72), and 20q13 (D20S100; LOD 1.75). For early-onset polyarticular

disease, evidence of linkage was found at chromosome 7q11 (D7S502; LOD

3.47). For pauciarticular disease, evidence supporting linkage was

observed on chromosome 19p13 (D19S216; LOD 2.98), the same marker that

supported linkage to the " JRA " phenotype. Other regions supporting

linkage with JRA disease subtype included 20q13, 4q24, 12q24, and Xp11.

Stratification of families based on the presence of the HLA-DR8 allele

in affected siblings resulted in significant linkage observed at 2p25

(D2S162/D2S305; LOD 6.0). CONCLUSION: These data support the hypothesis

that multiple genes, including at least 1 in the HLA region, influence

susceptibility to JRA. These findings for JRA are consistent with

findings for other autoimmune diseases and support the notion that

common genetic regions contribute to an autoimmune phenotype.

PMID: 15457461

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

5457461 & dopt=Abstract

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