Lack of association between genotypes or haplotypes of ADRB2 and Juvenile Idiopathic Arthritis. G. Pont-Kingdon1, K. Sumner1, B. Clifford3, A. Whiting3, E. Lyon1,2, J. Bohnsack3, S. Prahalad3 1) Institute for Clinical and Experimental Pathology, ARUP Laboratories, Salt Lake City, UT; 2) Pathology Dept, University of Utah, Salt Lake City, UT; 3) Pediatrics Dept, University of Utah, Salt Lake City, UT.
The 2 adrenergic receptor (2-AR) is present in numerous cell types and ADRB2 polymorphism(s) has been associated with asthma severity, response to beta agonist drugs, and rheumatoid arthritis (RA). The 2-AR has also been shown to contribute to the initiation and progression of joint damage in animals with experimental arthritis.. Our objective was to investigate ADRB2 variants for association with juvenile idiopathic arthritis (JIA) or major JIA subtypes. SNPs at position 46 and 79 result in substitution of glycine to arginine at position 16 (G16R), and of glutamine to glutamic acid at position 27 (E27Q). Both of these have been shown to have functional consequences. ADRB2 haplotypes were established in a cohort of 348 children with JIA and 448 autoimmunity free controls matched for ethnicity by direct molecular haplotyping using melting-curve analysis of a fluorescently labeled loci-spanning probe (LSProbe) that analyzed both SNPs simultaneously. Both ADRB2 SNPs were in Hardy-Weinberg equilibrium among controls. The minor allele frequencies in the controls at positions 16 and 27 were 36.7 % and 41.1% respectively. No association was found between JIA and the genotypes of the 2 ADRB2 SNPs as well as ADRB2 haplotypes. Specifically the haplotype that demonstrated a strong association with RA (R16-Q27) was not associated with JIA (36.7 % among cases, 38.3% among controls). Furthermore none of the variants demonstrated association after stratification by JIA subtypes, including the rheumatoid factor positive polyarticular JIA, although the number of patients with this subtype (~9%)was underpowered to replicate results in adults with RA. Our results indicate that ADRB2 variants are not associated with JIA or major JIA subtypes. These observations suggest that although they share several clinical and pathological features, JIA and RA have unique genetic associations.