Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement

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


About Half of S100 Cluster Genes On Chromosome 1q21.1 Are up-Regulated in the RA, SLE, Polyarticular Type Juvenile Idiopathic Arthritis (polyJIA), and Systemic-Onset JIA (sJIA)

Sugino1,  Hidehiko, Aoki2,  Chieko, Lee1,  Hooi-Ming, Adachi2,  Yasuo, Matsubara3,  Kenichi, Ochi4,  Takahiro, Nishimoto2,  Norihiro

Osaka University, Osaka, Japan
Wakayama Medical University, Osaka, Japan
DNA Chip Research Inc., Kanagawa, Japan
Osaka Police Hospital, Osaka, Japan

Purpose:

Back ground: S100 gene family encodes the EF-hand super-family of calcium binding proteins including at least 14 family members clustered relatively closely on chromosome 1q21.1. Recently, up-regulation of S100 proteins, S100A4, A8/9 and A12, in RA patients has been reported. Objective: To know the pathological roles of S100 proteins, we investigated the comprehensive gene expression profiling of 17 kinds of S100 proteins using DNA microarray in paptients with active RA, SLE, polyJIA, and sJIA. These 17 kinds of S100 proteins contain the clustered 14 molecules. Moreover, to clarify the molecular functions of S100 proteins in RA, we compared the amino acid sequence of up-regulated S100 proteins.

Method:

Total RNA was extracted from the peripheral blood obtained from 114 patients with RA, 12 patients with SLE, 6 patients with polyJIA, 51 patients with sJIA, and 53 healthy individuals, and used to prepare amino allylRNA (aRNA). aRNA was subjected to Cy3 and Cy5 labeling and hybridized with an oligonucleotide-based DNA microarray. The data among patients and healthy individuals were analyzed by parametric statistical group comparison. The amino acid sequences of S100 proteins were aligned by multi-sequence Clustal X analysis. Evolutionary trees were obtained by NJ analysis (1000 bootstrap).

Results:

S100A4, A6, A8/9, A11 and A12 are significantly up-regulated in RA and polyJIA compared to healthy controls. S100A6, A8/9, A11 and A12 were also up-regulated in SLE and sJIA. S100A4 was increased in the groups of RA and polyJIA but not in the groups of SLE and sJIA.Except for these six S100 proteins, other eleven S100 proteins remained stationary among the RA, SLE, sJIA, polyJIA and healthy controls. Phylogenetic tree of S100 proteins shows that the S100A8/9 and A12, which have been frequently reported in inflammation, recently branched off from the same origin and average percent similarity is 74.3%. In contrast, S100A4, A6 and A11 are diversified with each other in the amino acid levels.

Conclusion:

We confirmed the up-regulation of S100A4, A8/9 and A12 in RA and newly found the up-regulation of S100A6 and A11 in RA, SLE, polyJIA and sJIA. All the genes are encoded by human chromosome1q21.1. The structural similarities and diversifications among the 6 kinds of S100 proteins, which up-regulated in RA patients, may reflect the different contributions to the etiologies of RA.

To cite this abstract, please use the following information:
Sugino, Hidehiko, Aoki, Chieko, Lee, Hooi-Ming, Adachi, Yasuo, Matsubara, Kenichi, Ochi, Takahiro, et al; About Half of S100 Cluster Genes On Chromosome 1q21.1 Are up-Regulated in the RA, SLE, Polyarticular Type Juvenile Idiopathic Arthritis (polyJIA), and Systemic-Onset JIA (sJIA) [abstract]. Arthritis Rheum 2009;60 Suppl 10 :739
DOI: 10.1002/art.25819

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