Genome-wide single nucleotide polymorphism analyses of rheumatoid arthritis.
Because of the limitations of candidate gene studies and linkage analyses for common diseases, genome-wide association studies are now recognized as a powerful approach to mapping responsible genes with modest effects on various diseases. We performed whole genome case-control linkage disequilibrium (LD) mapping for rheumatoid arthritis (RA)-associated genes in Japanese subjects using single nucleotide polymorphisms (SNPs) mainly discovered in gene-containing regions. We identified RA-associated polymorphisms in two genes/loci, PADI4 and SLC22A4/A5 cluster. PADI4 catalyzes the conversion of arginine residues to citrulline in proteins. Recent reports on the high specificity of autoantibodies against citrullinated proteins to RA and the results of our study suggest that citrullination by PADI4 is a fundamental phenomenon of RA. On the other hand, the functions of SLC22A4/A5 have not been studied in detail, but SLC22A4/A5 have been reported to have multiple polymorphisms associated with several autoimmune diseases. Thus, large-scale LD mapping appears to be effective for identifying RA-associated polymorphisms.
Yamamoto
Kazuhiko
K
Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Tokyo 113-0033, Japan. yamamoto-tky@umin.ac.jp
Yamada
Ryo
R
D001172:Arthritis, Rheumatoid / Q000235:genetics*; D015894:Genome, Human; D006801:Humans; D006867:Hydrolases / Q000235:genetics; D027701:Organic Cation Transport Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases; D000074058:Solute Carrier Family 22 Member 5; D027981:Symporters
D027701:Organic Cation Transport Proteins; C109807:SLC22A4 protein, human; C492020:SLC22A5 protein, human; D000074058:Solute Carrier Family 22 Member 5; D027981:Symporters; D006867:Hydrolases; C000629235:PADI4 protein, human; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases