BIOMAT Database Logo BIOMAT Database Logo

Association of the PTPN22 R620W polymorphism with anti-topoisomerase I- and anticentromere antibody-positive systemic sclerosis. 2006

Pravitt Gourh, and Filemon K Tan, and Shervin Assassi, and Chul W Ahn, and Terry A McNearney, and Michael Fischbach, and Frank C Arnett, and Maureen D Mayes
University of Texas Health Science Center at Houston, TX 77030, USA. pravit.gourh@uth.tmc.edu

OBJECTIVE To determine any associations of the PTPN22 R620W single-nucleotide polymorphism (SNP) with systemic sclerosis (SSc) or with anticentromere antibody (ACA)-positive or anti-topoisomerase I (anti-topo I) antibody-positive SSc, in a case-control study of US white, black, Hispanic, and Choctaw Indian individuals. METHODS A total of 850 white, 130 black, 120 Hispanic, and 20 Choctaw Indian patients with SSc were compared with 430 white, 164 black, 146 Hispanic, and 76 Choctaw Indian control subjects, respectively. All subjects were living in the US. PTPN22 SNP (rs2476601) genotyping was performed by TaqMan 5' allelic discrimination assay and pyrosequencing. RESULTS The PTPN22 CT/TT genotype showed significant association with anti-topo I antibody-positive SSc in white patients (odds ratio [OR] 2.21, 95% confidence interval [95% CI] 1.3-3.7) and with ACA-positive white patients with SSc (OR 1.70, 95% CI 1.1-2.7). Frequency of the PTPN22*T allele also showed significant association with anti-topo I antibody-positive SSc in white patients (OR 2.03, 95% CI 1.3-3.2). When data for patients in the 3 ethnic groups (black, white, and Hispanic) were combined, a significant association with both genotype and allele frequencies was observed, suggesting a trend toward association in ACA-positive and anti-topo I antibody-positive SSc. Stepwise logistic regression analysis (controlled for the confounding effects of sex and race) showed that the PTPN22 CT/TT genotype was associated with a significantly higher risk of SSc compared with the CC genotype (for patients with SSc, OR 1.64, 95% CI 1.2-2.2; for ACA-positive patients with SSc, OR 1.63, 95% CI 1.0-2.6; for anti-topo I antibody-positive SSc, OR 2.33, 95% CI 1.5-3.7). CONCLUSIONS Our results indicate that the PTPN22 R620W polymorphism is associated with ACA-positive and anti-topo I antibody-positive subsets of SSc and represents a risk factor in both white patients and black patients. The association of subsets of SSc with the PTPN22 R620W polymorphism further strengthens the classification of SSc within the spectrum of autoimmune diseases and strongly suggests the involvement of common susceptibility genes and similarly disordered immunoregulatory pathways.

UI MeSH Term Description Entries
D008297 Male Males
D002503 Centromere The clear constricted portion of the chromosome at which the chromatids are joined and by which the chromosome is attached to the spindle during cell division. Centromeres
D004264 DNA Topoisomerases, Type I DNA TOPOISOMERASES that catalyze ATP-independent breakage of one of the two strands of DNA, passage of the unbroken strand through the break, and rejoining of the broken strand. DNA Topoisomerases, Type I enzymes reduce the topological stress in the DNA structure by relaxing the superhelical turns and knotted rings in the DNA helix. DNA Nicking-Closing Protein,DNA Relaxing Enzyme,DNA Relaxing Protein,DNA Topoisomerase,DNA Topoisomerase I,DNA Topoisomerase III,DNA Topoisomerase III alpha,DNA Topoisomerase III beta,DNA Untwisting Enzyme,DNA Untwisting Protein,TOP3 Topoisomerase,TOP3alpha,TOPO IIIalpha,Topo III,Topoisomerase III,Topoisomerase III beta,Topoisomerase IIIalpha,Topoisomerase IIIbeta,DNA Nicking-Closing Proteins,DNA Relaxing Enzymes,DNA Type 1 Topoisomerase,DNA Untwisting Enzymes,DNA Untwisting Proteins,Topoisomerase I,Type I DNA Topoisomerase,III beta, Topoisomerase,III, DNA Topoisomerase,III, Topo,III, Topoisomerase,IIIalpha, TOPO,IIIalpha, Topoisomerase,IIIbeta, Topoisomerase,Topoisomerase III, DNA,Topoisomerase, TOP3,beta, Topoisomerase III
D005260 Female Females
D005838 Genotype The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS. Genogroup,Genogroups,Genotypes
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001323 Autoantibodies Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them. Autoantibody
D012307 Risk Factors An aspect of personal behavior or lifestyle, environmental exposure, inborn or inherited characteristic, which, based on epidemiological evidence, is known to be associated with a health-related condition considered important to prevent. Health Correlates,Risk Factor Scores,Risk Scores,Social Risk Factors,Population at Risk,Populations at Risk,Correlates, Health,Factor, Risk,Factor, Social Risk,Factors, Social Risk,Risk Factor,Risk Factor Score,Risk Factor, Social,Risk Factors, Social,Risk Score,Score, Risk,Score, Risk Factor,Social Risk Factor
D012595 Scleroderma, Systemic A chronic multi-system disorder of CONNECTIVE TISSUE. It is characterized by SCLEROSIS in the SKIN, the LUNGS, the HEART, the GASTROINTESTINAL TRACT, the KIDNEYS, and the MUSCULOSKELETAL SYSTEM. Other important features include diseased small BLOOD VESSELS and AUTOANTIBODIES. The disorder is named for its most prominent feature (hard skin), and classified into subsets by the extent of skin thickening: LIMITED SCLERODERMA and DIFFUSE SCLERODERMA. Sclerosis, Systemic,Systemic Scleroderma,Systemic Sclerosis
D013781 Texas State bounded on the north by Oklahoma, on the east by Arkansas and Louisiana, on the south by Mexico, and on the west by New Mexico.

Related Publications

Pravitt Gourh, and Filemon K Tan, and Shervin Assassi, and Chul W Ahn, and Terry A McNearney, and Michael Fischbach, and Frank C Arnett, and Maureen D Mayes
Lack of association of the PTPN22 gene polymorphism R620W with systemic sclerosis.
January 2006, Clinical and experimental rheumatology,
Pravitt Gourh, and Filemon K Tan, and Shervin Assassi, and Chul W Ahn, and Terry A McNearney, and Michael Fischbach, and Frank C Arnett, and Maureen D Mayes
Association of the PTPN22*R620W polymorphism with autoimmune myasthenia gravis.
February 2006, Annals of neurology,
Pravitt Gourh, and Filemon K Tan, and Shervin Assassi, and Chul W Ahn, and Terry A McNearney, and Michael Fischbach, and Frank C Arnett, and Maureen D Mayes
Association of Anti-Topoisomerase I Antibodies of the IgM Isotype With Disease Progression in Anti-Topoisomerase I-Positive Systemic Sclerosis.
November 2020, Arthritis & rheumatology (Hoboken, N.J.),
Pravitt Gourh, and Filemon K Tan, and Shervin Assassi, and Chul W Ahn, and Terry A McNearney, and Michael Fischbach, and Frank C Arnett, and Maureen D Mayes
No association of PTPN22 R620W gene polymorphism with rheumatic heart disease and systemic lupus erythematosus.
November 2011, Molecular biology reports,
Pravitt Gourh, and Filemon K Tan, and Shervin Assassi, and Chul W Ahn, and Terry A McNearney, and Michael Fischbach, and Frank C Arnett, and Maureen D Mayes
The PTPN22 R620W polymorphism in anti-neutrophil cytoplasmic antibody-associated vasculitis in Mexican Mestizos.
December 2016, Rheumatology (Oxford, England),
Pravitt Gourh, and Filemon K Tan, and Shervin Assassi, and Chul W Ahn, and Terry A McNearney, and Michael Fischbach, and Frank C Arnett, and Maureen D Mayes
Evaluation of the genetic association of the PTPN22 R620W polymorphism in familial and sporadic systemic lupus erythematosus.
August 2006, Arthritis and rheumatism,
Pravitt Gourh, and Filemon K Tan, and Shervin Assassi, and Chul W Ahn, and Terry A McNearney, and Michael Fischbach, and Frank C Arnett, and Maureen D Mayes
RXRB Is an MHC-Encoded Susceptibility Gene Associated with Anti-Topoisomerase I Antibody-Positive Systemic Sclerosis.
September 2017, The Journal of investigative dermatology,
Pravitt Gourh, and Filemon K Tan, and Shervin Assassi, and Chul W Ahn, and Terry A McNearney, and Michael Fischbach, and Frank C Arnett, and Maureen D Mayes
PTPN22 R620W polymorphism is not associated with pemphigus.
November 2007, The British journal of dermatology,
Pravitt Gourh, and Filemon K Tan, and Shervin Assassi, and Chul W Ahn, and Terry A McNearney, and Michael Fischbach, and Frank C Arnett, and Maureen D Mayes
Elevation of IgG levels is a serological indicator for pulmonary fibrosis in systemic sclerosis with anti-topoisomerase I antibodies and those with anticentromere antibody.
May 2008, Clinical and experimental dermatology,
Pravitt Gourh, and Filemon K Tan, and Shervin Assassi, and Chul W Ahn, and Terry A McNearney, and Michael Fischbach, and Frank C Arnett, and Maureen D Mayes
The PTPN22 R620W polymorphism is not associated with systemic rheumatic diseases in South Africans.
April 2010, Rheumatology (Oxford, England),
Copied contents to your clipboard!