title: Association of PTPN22 single nucleotide polymorphism with rheumatoid arthritis but not with allergic asthma.
abstract: PTPN22 gene encodes a lymphoid tyrosine phosphatase (LYP), an important negative regulator of T-cell responses. The 1858C>T (Arg620Trp) single nucleotide polymorphism (rs2476601) was found associated with autoimmune diseases, including rheumatoid arthritis (RA). Allergic diseases are similar to autoimmune diseases, by an exaggerated immune response to an antigen (allergen in this case) normally not invoking such response in healthy individuals. We investigated whether polymorphism 1858C>T in PTPN22 gene is associated with susceptibility to allergic asthma and RA in a Polish population. PTPN22 was genotyped in 173 patients with RA, in 198 patients with allergic asthma, and in 543 controls using PCR-RFLP. The patients with RA differed from healthy controls in frequencies of PTPN22 1858C>T alleles (P=0.0004; odds ratio (OR), 1.8; 95% CI, 1.33-2.55) and genotypes (P=0.0009). Strong associations of 1858T allele with RA limited to joints (0.21 vs 0.12, P=0.0002; OR, 2.1; 95% CI, 1.44-3.00), with erosive disease (0.20 vs 0.12, P=0.0003; OR, 1.92; 95% CI, 1.34-2.71), with a lack of rheumatoid factor (RF; 0.23 vs 0.12, P=0.0008; OR, 2.29; 95% CI, 1.44-3.63), and weak association with the presence of RF (0.17 vs 0.12, P=0.02; OR, 1.6; 95% CI, 1.10-2.40) in comparison with healthy controls were observed. Very strong association of 1858T allele (P<0.0001; OR, 2.72; 95% CI, 1.9-3.9) and T phenotype (P<0001; OR, 3.2; 95% CI, 2.1-4.9) with antibodies to cyclic citrullinated peptide (CCP) was found. When patients with allergic asthma were typed for PTPN22 1858C>T polymorphism, no difference with control was found. Subdivision of patients into those with mild, moderate, or severe asthma did not reveal any associations. In conclusion, we confirmed associations between several clinical manifestations of RA and PTPN22 1858T allele. However, no association with 1858C>T polymorphism was found for susceptibility to allergic asthma or for severity of the disease.
authors.affiliation: Laboratory of Immunogenetics, Department of Clinical Immunology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.
authors.forename: Edyta
authors.initials: E
authors.lastname: Majorczyk
authors.forename: Monika
authors.initials: M
authors.lastname: Jasek
authors.forename: Rafał
authors.initials: R
authors.lastname: Płoski
authors.forename: Marta
authors.initials: M
authors.lastname: Wagner
authors.forename: Anna
authors.initials: A
authors.lastname: Kosior
authors.forename: Andrzej
authors.initials: A
authors.lastname: Pawlik
authors.forename: Andrzej
authors.initials: A
authors.lastname: Obojski
authors.forename: Wioleta
authors.initials: W
authors.lastname: Luszczek
authors.forename: Izabela
authors.initials: I
authors.lastname: Nowak
authors.forename: Andrzej
authors.initials: A
authors.lastname: Wiśniewski
authors.forename: Piotr
authors.initials: P
authors.lastname: Kuśnierczyk
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001172:Arthritis, Rheumatoid / Q000201:enzymology* / Q000235:genetics*; D001249:Asthma / Q000201:enzymology* / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011044:Poland; D020641:Polymorphism, Single Nucleotide; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics*
chemical_list: C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22