Association of STAT4 rs7574865 and PTPN22 rs2476601 polymorphisms with rheumatoid arthritis and non-systemically reacting antibodies in Egyptian patients

Abstract

The aim of this study was to investigate association of protein tyrosine phosphatase non-receptor type 22 (PTPN22) rs2476601 and signal transducer and activator of transcription 4 (STAT4) rs7574865 polymorphisms with rheumatoid arthritis (RA) susceptibility and to assess potential association with the status of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies, serum neopterin, and disease activity. RF, anti-CCP antibodies, and neopterin were assayed in serum of 100 unrelated RA patients and 114 controls. STAT4 rs7574865 G/T and PTPN22 rs2476601 C/T polymorphisms were genotyped by the TaqMan allelic discrimination method. The frequency of STAT4 variant allele was significantly higher in RA patients than in controls (p = 0.01), while the variant allele of PTPN22 was identified in only two RA patients, in a heterozygous form and in none of control subjects. The frequency of STAT4 variant allele carrier genotypes (GT+TT) was significantly higher among RA patients than in controls (43.7 vs. 10.5%, p = 0.02) and associated with RA under additive and dominant models. The frequency of RF and anti-CCP positivity was significantly higher among RA patients carrying T allele genotypes compared to patients carrying wild genotype (P = 0.02 and 0.04, respectively). No significant associations between STAT4 variant and serum neopterin or disease activity parameters were identified. Our study confirmed the association of STAT4 rs7574865 polymorphism with RA and was the first to indicate an association with RF and anti-CCP antibodies positivity. We also found PTPN22 rs2476601 has no role in susceptibility to RA in Egyptian patients.

Neopterin serum level does not reflect the disease activity in rheumatoid arthritis: A systematic review and meta‐analysis

“…Ultimately, of 98 articles screened, 15 studies met the eligibility criteria. [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] The characteristics of the included studies are described in Table 1, and the study selection process is given in Figure 1.…”

“…Twenty‐three studies have been selected for full‐text analysis; after securitization of them, eight studies were excluded due to the lack of sufficient data or similar results that were also reported in other publications. Ultimately, of 98 articles screened, 15 studies met the eligibility criteria 17–31 . The characteristics of the included studies are described in Table 1, and the study selection process is given in Figure 1.…”

PTPN22 gene polymorphism and susceptibility to rheumatoid arthritis (RA): Updated systematic review and meta‐analysis

“…Finally, 45 publication containing 23584 cases and 24497 healthy controls were identified as eligible publications for meta‐analyzing the association of the PTPN22 gene rs2476601 polymorphism and RA susceptibility. Of these 45 publication, 26 publications were conducted in Caucasians, 3,28–52 eight publications were in Asian countries, 53–60 seven publications were in African countries 61–67 and five publications were in countries with mixed ethnicity, which included Africans, Latins, American‐Africans and Caucasians 10,68–70 . Among the included studies, Rodriguez et al 46 evaluated the association of the PTPN22 gene rs2476601 SNP and RA in six countries (Spain, New Zealand, Norway, Germany, UK and The Netherlands), although the results were reported in one article; therefore, we enumerated this as one eligible publication.…”

rs2476601 in PTPN22 gene in rheumatoid arthritis and periodontitis—a possible interface?

“…Patients presenting the T allele of rs2476601 in PTPN22 gene were significant more often affected by RA regardless of their periodontal status (Table 3 ). In different case–control studies the influence of this genetic variant on the etiology of RA was discussed controversially [ 44 , 45 ]. However, the results presented here are in accordance with a large scale meta-analysis where the T allele [ 6 , 20 ] was associated with RA susceptibility.…”