Association of PTPN22 1858C→T polymorphism, HLA-DRB1 shared epitope and autoantibodies with rheumatoid arthritis.
To assess impact of PTPN22 1858C→T polymorphism, HLA shared epitope and autoantibodies on susceptibility and severity of rheumatoid arthritis (RA). A total of 150 RA patients and 150 controls were included in the study. Anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factor isotypes (IgG, IgM and IgA) were assayed by ELISA. PTPN22 1858C→T polymorphism was performed by RFLP analysis and HLA-DRB1 genotyping by PCR-SSP analysis. Single-view, anteroposterior radiographs of the hands and feet were obtained on all RA patients. The results showed association of PTPN22 1858 T allele with RA (OR = 2.3, 95 % CI 1.5-3.5) and bone erosion (OR = 2.9, 95 % CI 1.1-7.6). The associations increased with the combination of positive autoantibodies, HLA-DRB1 SE with PTPN22 1858 T allele carriage. The highest association was with the combination with anti-CCP antibodies (OR = 47.3, 95 % CI 10.9-204.4 for RA and OR = 69.4, 95 % CI 15.8-305.5 for erosion p < 0.001). Combination of PTPN22 1858 T allele carriage with negative RF isotypes or with absence HLA-DRB1 SE showed no significant association with RA. The presence of PTPN22 1858C→T polymorphism with HLA SE and autoantibodies increases risk of RA development and erosive disease.
Internal Medicine Department, National Research Centre, El Buhouth street 2311, Dokki, Egypt. halamzr@yahoo.com.
Hala M
HM
Raslan
Clinical and Chemical Pathology Department, National Research Centre, El Buhouth street 2311, Dokki, Egypt.
Hanaa R
HR
Attia
Community Medicine Research Department, National Research Centre, El Buhouth street 2311, Dokki, Egypt.
Iman
I
Salama
Clinical and Chemical Pathology Department, National Research Centre, El Buhouth street 2311, Dokki, Egypt.
Mona Hamed
MH
Ibrahim
Clinical and Chemical Pathology Department, National Research Centre, El Buhouth street 2311, Dokki, Egypt.
Eman Mahmoud
EM
Hassan
Biological Anthropology Department, National Research Centre, El Buhouth street 2311, Dokki, Egypt.
Mohamed S
MS
El Hussieny
Internal Medicine Department, Kasr Al Aini Hospital, Kasr Al Aini street, Cairo, Egypt.
Manal M
MM
El Menyawi
Medical Molecular Genetic Department, National Research Centre, El Buhouth street 2311, Dokki, Egypt.
Khalda S
KS
Amr
D000328:Adult; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D059811:HLA-DRB1 Chains / Q000276:immunology*; D006801:Humans; D007132:Immunoglobulin Isotypes; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics*; D012217:Rheumatoid Factor / Q000276:immunology
D001323:Autoantibodies; D000939:Epitopes; D059811:HLA-DRB1 Chains; D007132:Immunoglobulin Isotypes; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D012217:Rheumatoid Factor; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22
Autoantibodies; PTPN22 gene; Rheumatoid arthritis; Shared epitope