Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


TNIP2 Is Associated with Joint Destruction in Patients with Rheumatoid Arthritis.

Suzuki2,  Taku, Ikari2,  Katsunori, Yano2,  Koichiro, Toyama1,  Yoshiaki, Taniguchi2,  Atsuo, Yamanaka2,  Hisashi, Momohara2,  Shigeki

Department of Orthopaedic Surgery, Keio University
Institute of Rheumatology, Tokyo Woman's Medical University, Japan

Background:

Recently a large-scaled meta-analysis of genome-wide association studies (GWAS) and replication studies identified novel rheumatoid arthritis (RA) risk loci in European descent populations; CD2/CD58 (rs11586238), CD28 (rs1980422), PRDM1 (rs548234), TAGAP (rs394581), PTPRC (rs10919563), RAG1-TRAF6 (rs540386), PTPN2 (rs7234029), PLCL2 (rs4535211), CD247 (rs1773560), ICAM1-ICAM3 (rs892188), NHLH2 (rs4272626), TNIP2 (rs231707), REL (rs13017599), and BLK (rs13277113).

The aim of this study was to investigate the genetic association of these reported 14 genes and joint destruction in Japanese RA patients.

Materials and Methods:

DNA samples of 1504 Japanese patients were collected from the IORRA (Institute of Rheumatology RA cohort) DNA collection (84% of the patients were female, 87% were anticyclic citrullinated peptides (ACPA) antibody positive, 88% were rheumatoid factor positive and the mean age of the patients was 59.3 years). Of the patients, Sharp/ van der Heijde score (SHS) of the hands at 5-year disease duration, which represents joint destruction, could be measured in 628 patients.

Tested SNPs on the genes were selected based on the published studies (1–3). Genotyping was performed using the TaqMan assay according to the manufacture's instructions (Applied Biosystems, Japan). Multiple regression analysis was performed with SHS (hands) as a dependent variable, and as independent variables, the number of HLA-DRB1 alleles encoding the shared epitope (SE), the number of the risk alleles of RA-susceptible genes, sex, ACPA, and age of onset. The analysis was performed using the R software package.

Results:

Sex (female, P= 1.3×10-4), age of onset (younger, P= 1.3×10-4), the number of SE (P= 0.034), the risk allele of TNIP2 (P= 0.0092) had impact on radiographic joint damage in Japanese RA patients while the other RA-susceptible genes did not show any association with the joint destruction.

Conclusions:

We identified TNIP2 as a genetic factor for the joint destruction in RA patients.

1.Genetic variants at CD28, PRDM1 and CD2/CD58 are associated with rheumatoid arthritis risk. Nat Genet. (12):1313-8.

2. REL, encoding a member of the NF-kappaB family of transcription factors, is a newly defined risk locus for rheumatoid arthritis. Nat Genet. (7):820-3.

3. Replication of association between FAM167A (C8orf13)-BLK region and rheumatoid arthritis in a Japanese population. Ann Rheum Dis. (69):936-7.

To cite this abstract, please use the following information:
Suzuki, Taku, Ikari, Katsunori, Yano, Koichiro, Toyama, Yoshiaki, Taniguchi, Atsuo, Yamanaka, Hisashi, et al; TNIP2 Is Associated with Joint Destruction in Patients with Rheumatoid Arthritis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1611
DOI: 10.1002/art.29377

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