Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement

The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.


Association of Functional RANKL Promoter Polymorphisms with Subsets of Rheumatoid Arthritis (RA) in Taiwanese

Chen1,  Ji Yih, Wang1,  Chin-Man, Wu2,  J.

Chang Gung Memorial Hosp, Taoyuan, Taiwan
PhD, Birmingham

Purpose:

Rheumatoid arthritis (RA) is a common systemic autoimmune disease involving inflammation and destruction of joints. The aim of the current study was to investigate the functional implication of RANKL promoter polymorphisms and to examine whether RANKL promoter polymorphisms are associated with subtypes of RA in Taiwanese.

Method:

RANKL polymorphisms (4-bp deletion/insertion polymorphism and three promoter SNPs) were genotyped in 672 RA patients and 681 age-matched healthy controls from the same geographic region in Taiwan. Genotyping was carried out using gene scan and MALDI-TOF (Mass Array matrix-assisted laser desorption ionisation-time-of-flight mass spectrometry). Genotype distributions, allele and haplotypes frequencies were compared between RA and healthy controls as aggregates or as stratified by X-ray findings, autoantibody profile within patient groups. In addition, EMSA (Electrophoretic Gel Mobility Shift Assay) and promoter reporter assays were carried out to examine whether RANKL SNP -290A>G affects transcription factor binding and promoter function.

Results:

RANKL promoter SNP -290A>G significantly affected promoter activities. EMSA (Electrophoretic Gel Mobility Shift Assay) indicates that the SNP -290A>G is within a transcription element C/EBPb and that -290A allele has higher binding affinity for transcription factor C/EBPb. Notably, we observed a significant enrichment of -290GG genotype in C-spine involvement positive patients as compared with the C-spine negative RA patients (adjusted p = 0.012, OR 1.680 [95% CI 0.998–2.547]). Furthermore, the homozygotes -643 TT (adjusted p = 0.032 OR 1.967 [95% CI 1.148–3.037]) and -693 CC (adjusted p = 0.05, OR 1.680 [95% CI 0.998–2.547]) were significantly enriched in anti-CCP antibody positive patients compare to the anti-CCP negative RA patients. Haplotype 320/-290A was significantly reduced in RA (p = 0.034; odds ratio 0.689 [95% CI 0.488–0.973]) and destructive+ RA (p = 0.039; odds ratio 0.655 [95% CI 0.437–0.981]) patients as compared with normal controls. Haplotype 316/-643C and 316/-693G were significantly reduced in destructive+ RA patients as compared with destructive- RA patients (p = 0.026; odds ratio 0.558 [95% CI 0.331–0.939]. Among three RANKL SNPs haplotypes, haplotype -693G/-643C/-290A may have protective roles against CCP antibody production (p = 0.007; odds ratio 0.361 [95% CI 0.168–0.775]) and against destructive RA (p = 0.006; OR 0.354 [95% CI 0.163–0.769]).

Conclusion:

RANKL promoter SNP affected promoter functions and RA phenotypes. Our data suggest that RANKL may contribute to the complex disease process of RA in Taiwanese.

To cite this abstract, please use the following information:
Chen, Ji Yih, Wang, Chin-Man, Wu, J.; Association of Functional RANKL Promoter Polymorphisms with Subsets of Rheumatoid Arthritis (RA) in Taiwanese [abstract]. Arthritis Rheum 2009;60 Suppl 10 :396
DOI: 10.1002/art.25479

Abstract Supplement

Meeting Menu

2009 ACR/ARHP