Meta-analysis reveals an association of PTPN22 C1858T with autoimmune diseases, which depends on the localization of the affected tissue

• Published in: Genes and immunity Vol. 13; no. 8; pp. 641 - 652
• Main Authors: Zheng, J, Ibrahim, S, Petersen, F, Yu, X
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-12-2012; Nature Publishing Group
• Subjects: 631/208/457/649; 692/420/2489/144; 692/699/249/1313; Addison's disease; Alleles; Ankylosing spondylitis; Arthritis; Autoimmune diseases; Autoimmune Diseases - genetics; Autoimmune Diseases - immunology; Autoimmune Diseases - metabolism; Autoimmune Diseases - pathology; Biomedical and Life Sciences; Biomedicine; Cancer Research; Celiac disease; Cholangitis; Cirrhosis; Crohn's disease; Crohns disease; Development and progression; Diabetes; Diabetes mellitus; Disease; European Continental Ancestry Group; Gastrointestinal tract; Gastrointestinal Tract - immunology; Gastrointestinal Tract - metabolism; Gastrointestinal Tract - pathology; Gene Expression; Gene Frequency; Genes; Genetic aspects; Genetic polymorphisms; Genetic Predisposition to Disease; Graves disease; Health aspects; Human Genetics; Humans; Idiopathic thrombocytopenic purpura; Immune privilege; Immune System - immunology; Immune System - metabolism; Immune System - pathology; Immunology; Inflammatory bowel disease; Inflammatory bowel diseases; Kinases; Leukocytes (neutrophilic); Liver cirrhosis; Localization; Lupus; Meta-analysis; Multiple sclerosis; Mutation; Myasthenia; Myasthenia gravis; Myopathy; Neuromuscular junctions; Organ Specificity; original-article; Pathogenesis; Pemphigus; pemphigus vulgaris; Phosphatase; Phosphatases; Physiological aspects; Polymorphism; Polymorphism, Single Nucleotide; Primary biliary cirrhosis; Protein Tyrosine Phosphatase, Non-Receptor Type 22 - genetics; Protein-tyrosine-phosphatase; Proteins; Psoriasis; Reviews; Rheumatoid arthritis; Scleroderma; Skin - immunology; Skin - metabolism; Skin - pathology; Systemic lupus erythematosus; Systemic sclerosis; Thrombocytopenia; Ulcerative colitis; Uveitis; Vasculitis; Vitiligo; China; Italy; Europe; Germany; autoimmune diseases; meta-analysis; association; susceptibility gene; protein tyrosine phosphatase non-receptor type 22; target tissue
• ISSN: 1466-4879; 1476-5470
• DOI: 10.1038/gene.2012.46

Protein tyrosine phosphatase non-receptor type 22 (
PTPN22
) is a strong susceptibility gene shared by many autoimmune diseases. The aim of this study was to explore the mechanisms underlying this relationship. We performed a comprehensive analysis of the association between
PTPN22
polymorphism C1858T and autoimmune diseases. The results showed a remarkable pattern;
PTPN22
C1858T was strongly associated with type I diabetes, rheumatoid arthritis, immune thrombocytopenia, generalized vitiligo with concomitant autoimmune diseases, idiopathic inflammatory myopathies, Graves’ disease, juvenile idiopathic arthritis, myasthenia gravis, systemic lupus erythematosus, anti-neutrophil cytoplasmic antibody-associated vasculitis and Addison’s disease. By contrast,
PTPN22
C1858T showed a negligible association with systemic sclerosis, celiac disease, multiple sclerosis, psoriasis, ankylosing spondylitis, pemphigus vulgaris, ulcerative colitis, primary sclerosing cholangitis, primary biliary cirrhosis, Crohn’s disease and acute anterior uveitis. Further analysis revealed a clear distinction between the two groups of diseases with regard to their targeted tissues: most autoimmune diseases showing an insignificant association with
PTPN22
C1858T manifest in skin, the gastrointestinal tract or in immune privileged sites. These results showed that the association of
PTPN22
polymorphism with autoimmune diseases depends on the localization of the affected tissue, suggesting a role of targeted organ variation in the disease manifestations.