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

AbstractBackgroundRheumatoid 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 workTo 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 methods62 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.ResultsThe patients’ age was 42.7±12.7years, F:M (4.6:1) and a disease duration of 5.7±4.6years. 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 4–44.5ng/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; 4.1–33.9ng/ml), while in those with (677C>T) polymorphisms it was higher among those with CT genotype (8.9; 4.1–44.5).ConclusionSerum OPN level relates with the degree of rheumatoid activity

Atherosclerosis biomarkers in female systemic lupus erythematosus patients with and without cardiovascular diseases

Background: Cardiovascular diseases (CVD) and atherosclerosis are over presented in patients with systemic lupus erythematosus (SLE). Aim of the work: The aim of this study is to determine the frequency of some atherosclerosis biomarkers in SLE patients with and without CVD compared with controls. Patients and methods: 28 female SLE patients with a mean age of 30.1 ± 7.2 years and a history of CVD (SLE cases) were compared with 25 age matched SLE female patients but without a history of CVD (SLE controls) and 25 age matched population based control women (population controls). Intima, media thickness (IMT) was measured by B-mode ultrasound as a potential measure of atherosclerosis. Nontraditional biomarkers of atherosclerosis such as leptin, oxidized LDL (oxLDL) and homocysteine were also investigated. Results: SLE cases had significantly increased IMT compared with SLE controls and population controls (p < 0.001), whereas IMT of SLE controls did not differ from population controls. Compared to SLE controls, SLE cases had raised circulating levels of leptin (p < 0.001), homocysteine, dyslipidemia with raised triglycerides (p < 0.001), decreased HDL-cholesterol concentration, (p < 0.001), lupus anticoagulants (p = 0.01), and higher cumulative prednisone dose (p = 0.4). Disease duration was comparable between the two SLE groups and the blood pressure and body mass index (BMI) were similar among the 3 groups. Conclusion: A set of distinct CVD risk factors (biomarkers of atherosclerosis) separate SLE cases from SLE controls and normal population controls. If confirmed in a prospective study, they could be used to identify SLE patients at high risk of CVD in order to optimize treatment

Vascular endothelial growth factor G1612A (rs10434) gene polymorphism and neuropsychiatric manifestations in systemic lupus erythematosus patients

Abstract Aim: To investigate the relation between vascular endothelial growth factor (VEGF) gene polymorphism in systemic lupus erythematosus (SLE) patients and lupus related neuropsychiatric manifestations. Patients and methods: Sixty adult SLE patients recruited from the Rheumatology and Neurology departments of Cairo University hospitals were classified into two groups; Group A: 30 patients with neuropsychiatric manifestations (NPSLE) and Group B: 30 patients without. For both groups the SNP G1612A (rs10434) of the VEGF gene was genotyped by real time polymerase chain reaction (RT-PCR). Results: Statistically significant difference was found in genotype and allele frequencies between both groups (AA [70% vs 13.3%, p < 0.001] and GG [10% vs 66.7%, p < 0.001]). Conclusion: Polymorphism in the gene coding for VEGF may be associated with increased incidence of neuropsychiatric lupus in SLE patients

Urinary and tissue monocyte chemoattractant protein1 (MCP1) in lupus nephritis patients

Aim of the work: To assess the role of urinary and tissue monocyte chemoattractant protein-1 (MCP-1) in active lupus nephritis (LN) and to correlate the levels with disease activity and renal status. Patients and methods: Urinary and tissue MCP-1 were determined in 42 systemic lupus erythematosus (SLE) patients with LN. 20 matched controls were considered. SLE disease activity index (SLEDAI) was recorded in all patients. Urinary and renal tissue MCP-1 was evaluated. Renal biopsy was performed in active LN patients for histopathological classification and correlation. Results: 22 active LN patients (22.8 ± 4.7 years old) and 20 inactive (24.6 ± 4.3 years old) were studied. They were 39 female and 3 males (F:M 13:1). The urinary MCP-1 was significantly higher in active LN patients (1072.8 ± 658.4 pg/mg creatinine) compared to the inactive group (151.3 ± 103.5 pg/mg creatinine) and both were significantly higher than the level in the controls (19 ± 17.8 pg/mg creatinine) (p < 0.001). A significant correlation was present in the active LN patients between urinary MCP-1 level and proteinuria, anti-dsDNA, renal SLEDAI and biopsy activity index and negatively with C3 and C4. There was a significant correlation of the glomerular MCP-1 renal tissue expression score with the renal SLEDAI, anti-dsDNA, biopsy activity index and urinary MCP-1 and negatively with C3. Tubulointerstitial MCP-1 score significantly correlated with urinary MCP-1. Urinary, glomerular and tubular MCP-1 showed a sensitivity of 97%, 64% and 4% and specificity of 100%, 95% and 20% respectively in detecting LN. Conclusion: MCP-1 could be a valuable marker for LN and disease activity