RESEARCH - Association of the IL 4R single nucleotdie polymorphism I50V with rapidly erosive RA

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Arthritis Rheum. 2006 May;54(5):1491-500.

Association of the IL4R single-nucleotide polymorphism I50V with rapidly

erosive rheumatoid arthritis.

Prots I, Skapenko A, Wendler J, Mattyasovszky S, Yone CL, Spriewald B,

Burkhardt H, Rau R, Kalden JR, Lipsky PE, Schulze-Koops H.

Nikolaus Fiebiger Center for Molecular Medicine, Clinical Research Group

III, University of Erlangen-Nuremberg, Germany.

OBJECTIVE: To examine whether single-nucleotide polymorphisms (SNPs) of the

interleukin-4 receptor gene IL4R influence susceptibility to, or

radiographic progression in, rheumatoid arthritis (RA). METHODS: The

contribution of 2 SNPs (I50V and Q551R) in the coding region of IL4R to RA

susceptibility was analyzed by allele-specific polymerase chain reaction in

a case-control study of 471 RA patients and 371 healthy controls. Patients

with available radiographs of the hands and feet obtained 2 years after

disease onset (n = 302) were stratified retrospectively according to

radiologic outcome into an erosive and a nonerosive group to evaluate the

association between IL4R SNPs and disease progression. RESULTS: No

differences in the genotype and allele frequencies of the I50V or Q551R SNPs

were identified between the RA patients and healthy controls. In contrast,

significant differences in the distribution of I50V IL4R SNP genotypes

between patients with erosive and nonerosive disease were observed (chi(2) =

15.68, P = 0.0004). Bone erosions at 2 years after disease onset were

present in 68.1% of patients homozygous for the V50 allele compared with

37.0% of patients homozygous for the I50 allele (odds ratio 3.86, P <

0.0001). This association was independent of individual factors previously

associated with severe disease, such as rheumatoid factor or the HLA-DR

shared epitope. On a cellular level, the V50 allele conferred significantly

reduced responsiveness to interleukin-4, providing a possible mechanism for

the association of the I50V IL4R polymorphism with early erosions in RA.

CONCLUSION: Our data identify the I50V IL4R SNP as a novel genetic marker in

RA, showing high predictive value for early joint destruction.

PMID: 16646030

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

6646030

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