Methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms in rheumatoid arthritis patients: Correlation with serum osteopontin levels and disease activity

Background: Rheumatoid arthritis (RA) is a systemic, chronic inflammatory disease with genetic predisposition. Osteopontin (OPN) is overexpressed in RA and plays a key role in the perpetuation of synovitis. Not all RA patients show the same level of response to methotrexate (MTX) suggesting genetic variations in the drug-metabolizing enzymes. Aim of the work: To detect methylene-tetra-hydrofolate reductase (MTHFR) 677C/T and 1298A/C gene polymorphisms in RA patients treated with MTX and to investigate the relationship with serum OPN levels and disease activity. Patients and methods: 62 RA patients and 21 healthy controls were included. Serum OPN was measured using ELISA. Genotyping of MTHFR gene was carried out by polymerase chain reaction-restriction fragment length polymorphism. Disease activity score in 28 joints (DAS28) and the modified health assessment questionnaire (MHAQ) were assessed. Results: The patients' age was 42.7 +/- 12.7 years, F:M (4.6: 1) and a disease duration of 5.7 +/- 4.6 years. Their DAS28 was 4.1 +/- 1.6 and the MHAQ (median 1; range 0-2.3). Serum OPN levels in RA patients (median 8.8; range 4-44.5 ng/ml) were significantly higher than in control (5.6; 2.1-10.9) (p=0.002). In RA patients, serum OPN significantly correlated with the duration of morning stiffness (p=0.009), ESR (p<0.0001) and DAS28 (p<0.0001). MTHFR (677C>T) polymorphisms significantly correlated with MHAQ (p=0.012) while (1298A>C) polymorphisms significantly correlated with tender joint count (p=0.04). OPN levels were higher among patients with MTHFR (1298A/C) AC genotype (8.9; 4.1-33.9 ng/ml), while in those with (677C>T) polymorphisms it was higher among those with CT genotype (8.9; 4.1-44.5). Conclusion: Serum OPN level relates with the degree of rheumatoid activity. (C) 2016 Egyptian Society of Rheumatic Diseases. Publishing services provided by Elsevier B.V.