Peptidylarginine deiminase type 4: identification of a rheumatoid arthritis-susceptible gene.
Recent studies using linkage disequilibrium and SNPs uncovered a rheumatoid arthritis (RA)-susceptible haplotype in the gene encoding peptidylarginine deiminase (PADI) type 4. This gene is one of four known PADI genes that encode enzymes to change arginine into citrulline in proteins. Post-translational modifications of proteins, including peptidyl citrullination, are related to autoimmunity, and peptidyl citrulline is a known target of one of the most RA-specific autoantibodies. Further research on PADI4, its citrullination of native peptides, subsequent breakdown of tolerance, and the role of these peptides in the development of RA, is expected to bring a better understanding of autoimmunity and arthritis, and advancements in the medical care of RA.
Yamada
Ryo
R
Laboratory for Rheumatic Diseases, SNP Research Center, The Institute of Physical and Chemical Research, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa, 230-0045, Japan. ryamada@src.riken.go.jp
Suzuki
Akari
A
Chang
Xiotian
X
Yamamoto
Kazuhiko
K
D000818:Animals; D000906:Antibodies / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology / Q000502:physiology; D002956:Citrulline / Q000276:immunology / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006801:Humans; D006867:Hydrolases / Q000235:genetics* / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology; D010455:Peptides / Q000276:immunology; D011110:Polymorphism, Genetic; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases
D000906:Antibodies; D010455:Peptides; D002956:Citrulline; D006867:Hydrolases; C000629235:PADI4 protein, human; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases