Polymorphisms of MTHFR, PTPN22 and STAT4 Genes and Association to Inflammatory Markers in Rheumatoid Arthritis Patients
Author(s):
Zainab Dhiyaa Alkhateeb
Date: 08/10/2026
doi: https://doi.org/10.5281/zenodo.8425890
Abstract
Background: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder characterized by
persistent synovial inflammation, progressive joint destruction, and significant extra-articular
manifestation.
Aim: Investigation the association between genetic polymorphisms in MTHFR, PTPN22 and STAT4 genes
and inflammatory markers including rheumatoid factor (RF), C-reactive protein (CRP), interleukin-6 (IL
6), and tumor necrosis factor-alpha (TNF-α) in patients with RA in order to elucidate their role in disease
susceptibility, pathogenesis, and clinical expression.
Materials and methods: A total of 50 RA patients and 40 healthy control (HC) individuals were selected,
and subjected to sampling of venous blood that used molecularly to indicate genetic polymorphisms
restriction fragment length polymorphism analysis (RFLP-PCR) for MTHFR gene (rs1801131T>G) and
genotyping of the allele-specific tetra primers amplification refractory mutation system (T-ARMS-PCR)
for PTPN22 (rs2476601G>A) and STAT4 (rs7574865G>T) genes. Serologically, the obtained sera were
served for measurement rheumatoid factor (RF) by qualitative ELIZA, as well as C reactive protein (CRP),
interleukine-6 (IL-6), and tumor-necrosis factor-alpha (TNF-α) throughout the quantitative ELISA.
Results: Findings of RFLP-PCR revealed genetic polymorphism of MTHFR gene in RA patients through
increasing the prevalence and risk of TG genotype and G allele. On other hand, results of T-ARMS-PCR
determined the marked frequency and risk of GA genotype in PTPN22 gene of RA patients, with
significant elevation in prevalence of G allele and risk of A allele. For STAT4 gene, results of genotyping
frequency reported a significant increase in prevalence and risk of GT genotype, with marled prevalence
of G allele and risk of T allele. Among RA patients, serological results of RF (0.358640.0186), CRP
(330.3612.99pg/ml), IL-6(35.640.94ng/L), and TNF-α (173.164.22pg/ml) were significantly higher
than the values of HC individuals (0.18110.008, 101.133.1599pg/ml, 8.580.32ng/L, and
49.332.39pg/ml, respectively).
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