Association between methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C polymorphisms and essential hypertension: A systematic review and meta-analysis

ObjectiveMany studies have investigated the role of 5,10-methylenetetrahydrofolate reductase gene (MTHFR) C677T/A1298C polymorphisms in essential hypertension (EH), but results are inconclusive. The purpose of this meta-analysis was to clarify the effects of MTHFR C677T/A1298C polymorphisms on the risk of EH.MethodsElectronic databases were searched to identify relevant studies published until January 2014. Data were extracted by two independent authors. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the association between MTHFR C677T/A1298C polymorphisms and the risk of EH using random effect models or fixed effect models. Finally, 30 studies with 5207 cases and 5383 controls were included for C677T polymorphism and 6 studies with 1009 cases and 994 controls were included for A1298C polymorphism.ResultsMeta-analysis results indicated that MTHFR C677T polymorphism contributed to an increased risk of EH (for T vs. C: OR = 1.30, 95%CI = 1.18–1.43; for TT + CT vs. CC: OR = 1.34, 95%CI = 1.24–1.46; for TT vs. CC: OR = 1.62, 95%CI = 1.32–1.99; for TT vs. CT + CC: OR = 1.41, 95%CI = 1.26–1.59). However, no significant association was detected between MTHFR A1298C polymorphism and the risk of EH.ConclusionThis meta-analysis supports that MTHFR C677T polymorphism plays a role in developing EH. MTHFR A1298C polymorphism may not be associated with an increased risk of EH. Further large and well-designed studies are warranted to confirm these findings.     

The impact of fibromyalgia on disease assessment in rheumatoid arthritis patients

Aim of workTo explore the influence of the presence of concomitant fibromyalgia (FM) on the evaluation of disease activity score assessing 28 joints (DAS28), clinical disease activity index (CDAI) and modified health assessment questionnaire (MHAQ) in Egyptian patients with rheumatoid arthritis (RA).Patients and methodsThis study included 50 female RA patients; out of which 25 had concomitant FM (RAF group), the other 25 RA patients who served as controls did not have concomitant FM (RA group). All patients were subjected to an assessment of disease activity using the DAS 28 and the CDAI and assessment of functional outcome using MHAQ score.ResultsThe mean DAS 28 was significantly higher in RAF than RA patients (5.6 ± 1.1 versus 4.5 ± 1.3, P = 0.009). Also, the mean CDAI score was significantly higher in the RAF group (mean 23.3 ± 12.1 versus 13.7 ± 11.0, P = 0.002). The difference was attributed to significantly higher subjective items such as Tender joint count (TJC) and patient’s global assessment of general health (VAS-GH) in the RAF group. Mean MHAQ score was also higher in the RAF group (0.7 ± 0.6 versus 0.31 ± 0.4, P = 0.006).ConclusionFM is related to worse scores on the DAS28, CDAI and MHAQ in patients with RA. The presence of FM may have major implications in the interpretation of the DAS28 and CDAI scores because it is related to higher scores independently of objective evidence of RA activity.     

Sclerostin as an innovative insight towards understanding Rheumatoid Arthritis

BackgroundRheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joint inflammation leading to cartilage and local bone erosion. Sclerostin is a protein that in humans has been identified as an inhibitor of the pathway and leads to decreased bone formation.Aim of the workThis study aimed to investigate the level of serum sclerostin in RA patients, its association with inflammatory profile and its relation to disease activity and severity.Patients and methodsThirty-one Egyptian RA patients (28 females, 3 men) participated in this study. Their median age was 40 years. Disease activity score was assessed by the disease activity score (DAS28) and the functional status by the modified health assessment questionnaire (MHAQ). Ten matched controls were also included. Radiological severity was assessed according to the Larsen score. Serum sclerostin was measured.ResultsMedian serum sclerostin in RA patients was 2000 ng/dl (800–3300 ng/dl) which was significantly higher than in controls [210 ng/dl (150–2859)] (Z = −4.47, p < 0.001). Sclerostin significantly negatively correlated with C-reactive protein and DAS28 (p = 0.014 and p = 0.02 respectively) and positively correlated with the Larsen score and total joint count (p = 0.03 and p = 0.02 respectively). At serum level 267 ng/dl sclerostin has sensitivity of 96.8% to diagnose RA and a positive predictive value of 96.6%.ConclusionSerum sclerostin was significantly higher in RA patients than controls and correlated with disease activity and severity which highly suggests that it may play a role in the pathogenesis of RA making it a valuable new marker of monitoring the disease progress and prognosis.     

Anti-mutated citrullinated vimentin antibodies in rheumatoid arthritis patients: Relation to disease activity and manifestations

Aim of the workTo evaluate the frequency of anti-mutated citrullinated vimentin antibodies (MCV) in rheumatoid arthritis (RA) patients and to correlate it with disease activity and various disease manifestations.Patients and methodsFifty RA patients were recruited from the rheumatology and rehabilitation outpatient clinic, Kasr Al-Aini. Thirty healthy subjects served as controls. All patients were subjected to full history taking and clinical examination including general and joint assessment. Disease activity was assessed by the disease activity score (DAS-28) and functional ability was evaluated by the Modified Health Assessment Questionnaire (MHAQ). Anti-MCV and anti-cyclic citrullinated peptide (anti-CCP) were assayed by ELISA in patients and controls. Plain X-ray was performed on the hands and wrists and Sharp score was used to assess the erosions and joint space narrowing.ResultsA highly significant elevation of serum anti-MCV in RA patients (135.82 ± 126.81 U/ml) compared to controls (13.63 ± 8.48 U/ml) (p < 0.0001) was found. Anti-MCV showed a sensitivity of 84% and specificity of 80%. There was a significant difference between anti-MCV positive and anti-MCV negative patients as regards MHAQ (1.07 ± 0.74 vs. 0.52 ± 0.37, p = 0.005) and Sharp erosion score (12.93 ± 23.55 vs. 4 ± 2.2, p = 0.02). Anti-CCP showed a sensitivity of 70% and specificity of 100%. There was a significant difference between the specificities of both markers (p = 0.03). There was no significant correlation of the anti-MCV with the clinical manifestations, MHAQ, DAS28 or Sharp score. Anti-MCV significantly correlated with anti-CCP (p < 0.0001).ConclusionAnti-MCV test has a significant association with the functional disability and radiologic progression in RA and could be considered as a promising biomarker.     

Methylenetetrahydrofolate reductase C677T and methionine synthase A2756G gene polymorphisms and associated risk of cardiovascular diseases: A study from Jammu region

AimPotent risk factors at both genetic and non-genetic levels are accountable for susceptibility and instigation of different cardiovascular phenotypes. Recently, homocysteine is being identified as an important predictor for cardiovascular diseases. Homocysteine remethylation plays a key role in the synthesis of methionine and S-adenosine methionine. Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MTR) genes are known to regulate the homocysteine remethylation reaction and higher homocysteine level is significantly associated with diverse cardiovascular phenotypes. In this context, we aimed to carry out a study on the association of MTHFR (C677T) and MTR (A2756G) gene polymorphism with CVD in population of Jammu region of J&K state.Materials and methodsA total of 435 individuals were enrolled (195 CVD patients and 240 controls) for the case–control study. Genotyping of MTHFR C677T and MTR A2756G gene polymorphism was done by PCR-RFLP technique. Biochemical parameters were estimated by biochemical analyser.ResultsMetabolic variables such as serum LDL-C, TC and TG were significantly higher in patients (p < 0.0001), whereas serum HDL-C was higher in controls. Majority of the patients were having history of hypertension (57.44%; p < 0.0001) as a concomitant condition. The evaluation of genetic association showed that, MTHFR C6877T (OR: 8.89, 95% CI: 2.01–39.40) and MTR A2756G (OR: 1.48, 95% CI: 1.09–2.00) polymorphisms associated with higher risk of CVD.ConclusionThe present study reveals significant differences in nongenetic variables among patients and control as well as association of gene polymorphisms with CVD risk.     

Serum matrix metalloproteinase-3 in rheumatoid arthritis patients: Correlation with disease activity and joint destruction

Aim of the workThis study was designed to measure the serum level of matrix metalloproteinase-3 (MMP-3) in rheumatoid arthritis (RA) patients and its correlation with functional status, disease activity and joint damage.Patients and methodsThe study included 50 RA patients satisfying 2010 ACR/EULAR classification criteria recruited from Bani-Suef University Hospital and 20 controls. Functional disability was assessed according to Modified Health Assessment Questionnaire (MHAQ). Disease activity score in 28-joints (DAS28) and visual analogue scale (VAS) of pain were evaluated. Radiological joint damage was assessed by Van der Heijde-modified Sharp Score (vdHSS). Serum levels of MMP-3 were measured for all subjects.ResultsRA patients (44 females and 6 males) had a mean age of 46.36 ± 13.63 years and disease duration of 5.6 ± 4.75 years. Serum MMP-3 levels were higher in patients than in controls (46.78 ± 46.99 versus 1.98 ± 1.71 ng/ml respectively, p = 0.0001) and significantly correlated with erythrocyte sedimentation rate (p = 0.001) and were significantly higher in patients with positive C-reactive protein, rheumatoid factor and anti-cyclic citrullinated peptide (p = 0.0001, p = 0.009, p = 0.042, respectively). MMP-3 significantly correlated with DAS28 (p = 0.0001) and vdHSS (r = 0.78, p = 0.0001) and a significant difference was shown in those with erosions compared to those without (p = 0.001). Serum MMP-3 levels significantly correlated negatively with cumulative steroid dose (r = −0.2, p = 0.03) and were significantly higher in patients who never received disease-modifying antirheumatic drugs (p = 0.001). There were no significant relations of MMP-3 with age, MHAQ, VAS for pain.ConclusionThese results indicate that serum MMP-3 is a measurable, useful specific marker of disease activity and joint damage in RA patients.     

Insulin resistance as a risk factor for subclinical atherosclerosis in rheumatoid arthritis

BackgroundInsulin resistance (IR) is strongly associated with systemic inflammation. Insulin resistance is known to be increased in patients with rheumatoid arthritis (RA) and has been shown to be a risk factor for both clinical cardiovascular disease and subclinical atherosclerosis.Aim of the workTo study the relationship between insulin resistance, disease activity and subclinical atherosclerosis in RA patients.Patients and methodsForty RA patients and twenty age and sex matched healthy individuals as controls were included. Patients with diabetes mellitus, obesity and hypertension were excluded. Fasting plasma sugar and serum insulin were done, RA disease activity was assessed using the disease activity score (DAS28) and IR was evaluated by the homeostasis model assessment (HOMA2). Carotid artery intima media thickness (IMT) was evaluated using ultrasound.ResultsRA patients had significantly higher erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) positivity, fasting plasma sugar and fasting serum insulin, HOMA2-IR levels than the controls. IR was present in 33 (82.5%) RA patients while it was present in only one (10%) of the controls (p = 0.001). RA patients with IR had significantly longer disease duration (p = 0.003), higher disease activity (p = 0.000), greater carotid IMT (p = 0.000), and more carotid plaques (p = 0.043) than those without insulin resistance. RA patients with increased IMT had significantly longer disease duration (p = 0.002), higher DAS28 score (p = 0.000) and higher HOMA2-IR (p = 0.000) than those with normal IMT.ConclusionsIn RA patients, IR significantly correlated with both disease activity and disease duration. Our study pointed out a significant association between IR and subclinical atherosclerosis in RA.     

The relationship of serum leptin levels with disease activity in Egyptian patients with rheumatoid arthritis

Aim of the workTo investigate whether serum leptin levels are elevated in patients with rheumatoid arthritis (RA) and whether these levels correlate with disease activity.Patients and methodsA case-control study was made on 37 patients with RA and 34 healthy control subjects. The following values were assessed for each patient: erythrocyte sedimentation rate (ESR), C reactive protein (CRP), rheumatoid factor (RF), swollen and tender joint counts, disease activity score 28 (DAS28), health assessment questionnaire score (HAQ), visual analog scale (VAS) of pain and serum leptin concentrations.ResultsPatients with RA had mild to moderate (DAS28 < 5.1) disease activity. The mean serum leptin in patients with RA (12.15 ± 11.48 ng/mL) was significantly higher (p < 0.001) than controls (3.99 ± 1.84 ng/mL). Serum leptin levels were significantly (p < 0.001) higher in female RA patients than in female controls. A nonsignificant difference (p = 0.41) was found between male patients with RA and male controls. Serum leptin levels were significantly (p < 0.001) higher in women than in men in both patients and controls. Serum leptin levels did not show correlation with age, disease duration, duration of morning stiffness, VAS, number of swollen and tender joints, DAS28, HAQ, ESR or CRP in patients with RA. Serum leptin levels were correlated positively with BMI in RA patients. The BMI was significantly higher (p < 0.001) in female than in male patients with RA.ConclusionAlthough leptin levels were higher in RA patients, there was no correlation with disease activity parameters, therefore, leptin levels cannot be used to reflect disease activity.     

Proteinase-activated receptor 2 expression on peripheral blood monocytes and T-cells in patients with rheumatoid arthritis

Aim of the workProteinase-activated receptor 2 (PAR2) is a G protein-coupled receptor activated by serine proteinases with proinflammatory activity. The aim of this work was to evaluate the expression of PAR2 on peripheral blood monocytes and T-cells in rheumatoid arthritis (RA) patients and its correlation with disease activity.Patients and methodsForty RA patients and 16 healthy controls were enrolled in this study. Flow cytometry was performed to detect PAR2 expression. Disease activity score (DAS28) was assessed.ResultsPAR2 expression was significantly higher on monocytes in RA patients with active disease compared with patients in remission and healthy controls (75.4 ± 7.68; 56 ± 13.93 and 46.5 ± 9.8 respectively; p < 0.001). It was higher in RA patients in remission compared to healthy control (p = 0.01). No significant difference was found between patients with moderate and high disease activity. It significantly correlated with the erythrocyte sedimentation rate (ESR) and DAS28 (p < 0.001). It was significantly higher in patients with rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) positivity (p = 0.01, p < 0.001, respectively). It was not significantly associated with C-reactive protein (CRP) positivity and was not significantly different between early and long standing RA patients. PAR2 expression on CD3⁺ T-cells was not significantly different between patients with RA disease activity, patients in remission and healthy controls. Also it was not significantly associated with the ESR, DAS28, anti-CCP, RF and CRP positivity.ConclusionPAR2 expression on monocytes is consistent with a pathogenic role for PAR2 in RA and suggests that PAR2 may have utility as a marker for RA disease activity.     

Assessment of synovitis in early rheumatoid arthritis by CXCL13 serum levels and power Doppler ultrasonography: Correlation with disease activity

Aim of the workAssessment of synovitis in rheumatoid arthritis (RA) is a major issue for proper treatment; it has been proven that high resolution ultrasound (US) examination could be of valuable help. The B-cell chemokine, CXCL13, is a proposed serum biomarker of synovitis in RA. We aimed to find out the presence of synovitis in patients with recent-onset RA and its correlation with disease activity.Patients and methodsWe evaluated 30 patients with early RA for the presence and degree of synovitis by performing high resolution US and obtaining serum CXCL13 levels. In addition, we correlated these results with disease activity score 28 (DAS 28). Results of high resolution US and serum CXCL13 were also obtained for 20 healthy age- and sex-matched volunteers and served as controls.ResultsSerum CXCL13 level was significantly increased in early RA patients vs. controls (p < 0.001). High resolution US revealed that RA patients had a significant increased synovial thickness and high power Doppler US score. In RA patients, DAS 28 had a significant correlation with serum CXCL13 (r = 0.42, p = 0.02), synovial thickness (r = 0.39, p = 0.03) and power Doppler US score (r = 0.43, p = 0.02). Serum CXCL13 level correlated with synovial thickness (r = 0.63, p = 0.001) and power Doppler US score (r = 0.69, p = 0.001).ConclusionRecent-onset RA patients suffer from synovitis as evidenced by significantly increased serum CXCL13 and by high resolution US. Serum CXCL13 is a reliable marker of synovial inflammation which correlates better with synovial thickening and power Doppler US scores than DAS28.     

Clinical significance of serum interleukin-6 and −174 G/C promoter polymorphism in Rheumatoid arthritis patients

Aim of the workTo evaluate the clinical significance of serum levels of interleukin-6 (IL-6) and ?174 G/C promoter polymorphism in Rheumatoid arthritis (RA) patients.Patients and methodsWe studied 37 RA patients and 10 age and gender matched healthy controls. Demographic, clinical and serological data were prospectively evaluated. Disease activity score (DAS28) and Health Assessment Questionnaire (HAQ) were assessed. Serum IL-6 level was measured and promoter (?174G/C) genotyped.ResultsSerum IL-6 levels were significantly higher in RA patients compared to control (p = 0.04), especially those with CC promoter polymorphism. Twenty-four patients had GG IL-6 (?174 G/C) gene promoter polymorphism, 11 were GC and 2 CC. Nine controls were GG and 1 GC. In patients with more advanced polymorphism (?174 CC) there was a significantly increased functional impairment (HAQ score) (p = 0.029) and platelet count (p = 0.049). In those with GG genotype, there was a significant correlation between IL-6 and Morning stiffness duration (r = 0.44,p = 0.03), while those with GC genotype had a significant negative correlation of the IL-6 level with the parameters of disease activity and the DAS28 (r = ?0.69,p = 0.019). None of the studied parameters would predict the IL-6 promoter polymorphism.ConclusionSerum IL-6 levels and ?174 G/C promoter polymorphism were higher in RA patients than in healthy controls. The inverse relation of IL-6 with the DAS28 in those with an increased IL-6 promoter polymorphism may confirm its increased involvement in the pathogenesis of RA and in the increased disease activity which may point to the need for considering of anti-IL-6 agents in their management plan.     

Autoantibodies to extractable nuclear antigens (ENAs) pattern in rheumatoid arthritis patients: Relevance and clinical implications

ObjectivesTo study the frequency of different autoantibodies to extractable nuclear antigens (ENAs) in rheumatoid arthritis (RA) patients and to correlate findings with clinical manifestations, disease activity and radiological damage.MethodsA total of 230 RA patients were included and 75 healthy controls. In all patients rheumatological assessment was done and routine laboratory investigations and immune profile were performed in both patients and controls, including: RF, ACPA, ANA and anti-ENAs (Ro/SSA, La/SSB, U1-RNP, anti-Jo-1 and anti-Sm). Radiological damage was scored using Sharp/van der Heijde, and disease activity was evaluated by DAS28-ESR and DAS28-CRP.ResultsRF was positive in 101 (43.9%), ACPA in 220 (95.7%), ANA in 58 (25.2%), anti Ro in 31 (13.5%), anti-La in 10 (4.3%), anti-Jo1 in 5 (2.2%) and anti-RNP in 2 (0.9%). Anti-Ro/SSA positively correlated with sicca symptoms (p = .02), RF titer (p < .001), ANA (p < .001), DAS28-ESR (p = .026), and DAS28-CRP (p = .003). Anti-La antibodies correlated positively with SJC (p = .001), TJC (p = .001), ANA (p < .001), DAS-28 ESR (p = .007). Anti-Jo-1 correlated positively with interstitial lung disease (ILD) (p ≤ .001), RF titer (p = .037) and ANA (p ≤ .001). Anti-RNP antibodies correlated positively with disease duration (p ≤ .001), ACPA titer (p ≤ .001) and ANA (p = .014). In the controls ANA was positive in two (2.7%), anti-Ro in three (4%), and none of the controls tested positive for other autoantibodies.ConclusionsIn RA patients, positive ANA is frequent and positively associated with anti-Ro, anti-La and anti-Jo1 autoantibodies. Screening for autoantibodies against other anti-ENAs seems mandatory in RA patients especially when ANA is positive. RA cases with positive Anti-Jo-1 may develop anti synthetase syndrome and ILD.     

Relation between plasma homocysteine, gene polymorphisms of homocysteine metabolism-related enzymes, and angiographically proven coronary artery disease

BackgroundHyperhomocyteinemia (HHcy) is a risk factor for coronary artery disease (CAD), and methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and methionine synthase reductase (MTRR) polymorphisms may contribute to plasma total homocysteine (tHcy) variation. We investigated the association of polymorphisms 1298A→C in the MTHFR gene, 2756A→G in the MTR gene, and 66A→G in the MTRR gene with tHcy levels and with CAD in patients undergoing coronary angiography.MethodsCAD patients (n = 151) and control subjects (n = 79) were compared regarding the prevalence of the polymorphisms, risk factors, and biochemical parameters.ResultsThe mean tHcy concentration was significantly higher in CAD patients than in control subjects (P < 0.001). HHcy (tHcy ≥ 15 μmol/l) conferred an OR of CAD of 4.1 (95% CI 2.2–7.5, P < 0.001). In both cases and controls, smokers had a higher tHcy level than non-smokers and demonstrated a markedly increased risk for CAD (OR = 2.5, 95% CI 1.7–3.3, P < 0.001). The allele frequencies of the MTHFR 1298A→C, MTR 2756A→G, and MTRR 66A→G mutations were 36.7%, 15.7%, and 36.6%, respectively. The 1298C allele frequency was significantly higher in the CAD group than in controls (P < 0.05) and showed a significant association with CAD in heterozygote carriers. There was no statistically significant difference between cases and controls in the frequencies of the A2756G alleles/genotypes in the MTR gene and of the A66G alleles/genotypes in the MTRR gene. The contributions to tHcy levels of the three common mutations were statistically significant. The heterozygosity of the MTHFR 1298AC genotype, MTR 2756G allele, and MTRR 66G allele yielded an OR of 3.4, 2.0, and 2.1, respectively, for having HHcy.ConclusionWe suggest that HHcy confers a risk for CAD, and smokers with tHcy are at a greatly increased risk. Our finding supports an important role of the MTHFR gene in CAD and provides evidence of polygenic regulation of tHcy.     

Osteoprotegerin (OPG) and Matrix Gla protein (MGP) in rheumatoid arthritis patients: Relation to disease activity

BackgroundImbalanced Matrix Gla protein (MGP) and Osteoprotegerin (OPG) levels occur in inflammatory diseases.Aim of the workThe aim of the present study was to evaluate serum MGP and OPG levels in Rheumatoid Arthritis (RA) patients and study their relation to the disease activity.Patients and methodsForty-five female RA patients and 45 age and sex-matched healthy controls were included in this study. Disease activity score 28-C-reactive protein (DAS28-CRP) was used for the assessment of disease activity. High-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), MGP and OPG were measured in patients and controls. The associations of MGP and OPG with DAS28-CRP and the other laboratory and clinical variables were analyzed.ResultsRA patients had significantly higher serum OPG levels (408.3 ± 520.9 pg/ml) and hs-CRP (2.8 ± 1.9 mg/l) than the control (92.5 ± 86.3 pg/ml and 0.9 ± 1.5 mg/l respectively) (p < 0.001 each). There was no significant difference in MGP levels between the patients and control (p = 0.3). The correlation of OPG and MGP with DAS28-CRP in the patients was insignificant (p = 0.4 and p = 0.8 respectively). Age positively correlated with OPG (r = 0.32, p = 0.02), but not with MGP concentration (r = 0.05, p = 0.64) in the RA patients.ConclusionsThe significant elevation of the OPG level in RA patients may through light on its possible role in the pathogenesis of this disease and could be considered as a future therapeutic target. The significant correlation with age suggests that OPG may be an important mediator especially in elderly RA cases.     

Methylenetetrahydrofolate reductase polymorphisms, C677T and A1298C, are associated with methotrexate-related toxicities in Korean patients with rheumatoid arthritis

We investigated associations between the methylenetetrahydrofolate reductase (MTHFR) polymorphisms C677T and A1298C and methotrexate (MTX)-related toxicities in Korean patients with rheumatoid arthritis (RA) taking MTX. One hundred sixty-seven patients with RA were enrolled in a cross-sectional study and genotyped for the single-nucleotide polymorphisms C677T and A1298C in MTHFR. Alleles, genotypes, and haplotypes of the C677T and A1298C polymorphisms were not associated with specific MTX toxicities. However, among RA patients with the 1298CC genotype, the proportion who experienced at least one toxicity was significantly greater than the proportion of patients with 1298AA who did (P?=?0.043). In addition, the proportion of patients with the 677C/1298A haplotype who experienced toxicity was greater than the proportion of those with 677C/1298C who did (P?=?0.032, odds ratio?=?2.085, 95% confidence interval 1.058–4.106). In this study, MTHFR polymorphisms were associated with MTX toxicities in Korean patients with RA. Further study for association of MTHFR polymorphisms with MTX toxicities should be needed in larger RA population.     

Significance of serum levels of angiopoietin-2 and its relationship to Doppler ultrasonographic findings in rheumatoid arthritis patients

BackgroundAngiopoietin-2 (Ang-2) is connected to angiogenesis in synovial regions, but the significance of its levels in patients with rheumatoid arthritis (RA) is still unclear.Aim of the workTo evaluate the significance of serum levels of Ang-2 in patients with RA. Also, to determine Ang-2 relationship to the findings of joints Doppler ultrasonographic findings.Patients and methodsThis study included 40 patients with RA, and 25 matched healthy controls. All patients were subjected to assessment of pain using visual analogue scale (VAS), assessment of personal activity using the Health Assessment Questionnaire (HAQ) score, and calculation of disease activity score (DAS 28). Laboratory assays of complete blood count (CBC), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF) titre, and measurement of serum levels of Ang-2 by ELISA. Doppler ultrasonography (US) assessment for eight joints, with calculation of synovial thickness and total signal score (TSS), was done.ResultsSerum Ang-2 levels were significantly higher among patients (3191.3 ± 594.9 pg/ml) than controls (1771.7 ± 103.1 pg/ml) (p < 0.001). Serum Ang-2 levels were significantly correlated with ESR, CRP, DAS28, and duration of morning stiffness (p < 0.001, p < 0.001, p < 0.001, and p = 0.025, respectively). There was a significant correlation between serum Ang-2 levels and findings of US, regarding joint synovial thickness, and TSS (p < 0.001, for both).ConclusionPatients with RA had significantly higher levels of serum Ang-2 versus controls. In those patients, serum Ang-2 levels were significantly correlated with disease activity markers (ESR, CRP), DAS28, and duration of morning stiffness. Moreover, these levels were significantly correlated with synovial thickness, and TSS. The role of Ang-2 in RA pathogenesis might open the door to the development of new therapeutic strategies, particularly which target angiogenesis.     

Assessment of health-related quality of life,anxiety and depression in patients with early rheumatoid arthritis

Aim of the workTo assess the effect of clinical manifestations, disease activity and medications on health-related quality of life (HRQoL) among patients with early rheumatoid arthritis (RA).Patients and methodsTwenty-six early RA patients (mean age 43.31 ± 10.51 years, disease duration: 16.5 ± 5.2 months) diagnosed according to the 2010 RA classification criteria were recruited from the outpatient clinic of the Rheumatology and Rehabilitation Department, Sohag University, and 22 age and sex matched healthy persons participated in a case control study. Demographic data were taken from all participants in the study. The 36-item short-form health survey (SF-36) and Hamilton Anxiety Rating Scale (HAM-A) were assessed as measures of HRQoL and psychiatric comorbidity for both patients and controls. Disease activity in RA was assessed using the disease activity score (DAS28). Scoring algorithms were applied to produce the physical and mental component scores (PCS and MCS).ResultsThere was statistically significant difference in the total SF36 score, anxiety and depression scores of HAM-A scale between patients and controls. The PCS showed the highest significant difference (p < 0.0001), followed by SF36 (p = 0.01) and MCS (p = 0.024). There were no significant differences according to the age, gender, occupation or level of education of the patients. Anxiety and depression scores significantly correlated with the bodily pain and DAS28 scores and inversely with the PCS and MCS. The DAS28 strongly negatively correlated with the PCS and MCS.ConclusionRheumatoid arthritis has a major impact on many areas of an individual’s life and tends to have a profound impact on the health-related quality of life.     

Serum level of interleukin-33 in rheumatoid arthritis patients and its association with bone erosion and interstitial lung disease

Aim of the workTo analyze the serum levels of IL-33 in RA patients and to investigate its relation to the clinical characteristics, laboratory investigations, joint erosions, functional status and disease activity. Its relation to the presence of interstitial lung disease (ILD) was well thought-out.Patients and methodsThe study included 50 RA patients and 30 matched control. Thorough clinical examination, investigations, disease activity score (DAS-28) and health assessment questionnaire (HAQ) were considered in the patients. Bone erosion was evaluated and interstitial lung disease (ILD) was identified on high-resolution computed tomography. The serum level of IL-33 was measured by enzyme-linked immunosorbent assay.ResultsSerum levels of IL-33 are significantly higher in RA patients (106.96 ± 52.6 pg/ml) than in healthy controls (46.9 ± 23 pg/ml) (p < 0.001). A significant correlation was found between IL-33 and the DAS28 (r = 0.4, p = 0.001), level of rheumatoid factor (r = 0.45, p = 0.001) and with the presence of ILD (r = 0.3, p = 0.04). There were no gender differences and the level did not significantly correlate with the age or disease duration. The medications received had no obvious effect on the IL-33 level. The level did not correlate with the HAQ. There was a significant correlation between the CT bone erosion scores the patient’s age, disease duration, rheumatoid nodules and DAS28. The erosion score also significantly correlated with the serum IL-33 levels in RA patients (r = 0.71, p = 0.001).ConclusionThese data support the hypothesis that IL-33 may be involved in RA pathogenesis and it may partly contribute to the bone erosion and ILD in RA patients.     

Significance of plasma osteopontin in diagnosis of hepatitis C virus-related hepatocellular carcinoma

Background and study aimsAlfa fetoprotein (AFP) is widely used as a surveillance test for hepatocellular carcinoma (HCC) among patients with liver cirrhosis (LC). However, the clinical use of AFP has been shown to present some important limitations in sensitivity and specificity. Osteopontin (OPN) is a secreted matrix glycoprotein that is emerging as a significant protein in the biology of HCC. The aim of this study was to assess the diagnostic value of plasma OPN compared with that of AFP in the diagnosis of HCC among hepatitis C virus (HCV)-related LC.Patients and methodsPlasma levels of OPN and AFP were measured in 69 Egyptian patients with HCV-related LC (35 with HCC and 34 without HCC) and 20 healthy controls.ResultsBoth median AFP and OPN levels were significantly higher in the HCC group compared to LC and healthy control groups (p < 0.001 in each) and in LC compared to the control group (p < 0.001). In the HCC group, both OPN and AFP levels were significantly higher in patients with Child–Pugh class C and B compared to class A (p < 0.05 in each). There was no correlation between OPN and AFP levels. The OPN level was significantly higher in patients with multiple focal lesions than in those with single lesions (p < 0.05) and in patients with portal vein invasion compared to patients without portal vein invasion (p < 0.05). Receiver operator characteristic (ROC) curves showed that the area under the curve (AUC) for OPN and AFP was 0.824 and 0.730, respectively.ConclusionOPN is a promising tumour marker which could be used as a screening test for the diagnosis of HCC in patients with LC and, hence, improves the prognosis and survival rate of these patients. The association of OPN with the multiplicity of focal lesions and portal vein invasion suggests an additional prognostic value.     

Levels of plasma cell-free DNA and its correlation with disease activity in rheumatoid arthritis and systemic lupus erythematosus patients

BackgroundCell free deoxyribonucleic acid (cf-DNA) is now emerging as a useful tool for non-invasive diagnostic methods related to a wide range of clinical conditions including autoimmune diseases.Aim of the workTo estimate the concentration of plasma cf-DNA in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) patients compared with healthy subjects and to correlate the results with clinical and laboratory parameters of disease activity.Patients and methodsThe study included 30 RA patients, 35 SLE patients and 25 matched control. Plasma cf-DNA was estimated by real-time quantitative PCR. Disease activity parameters for each disease were assessed; Disease Activity Score-28 (DAS28) was used for RA and SLE disease activity index 2000 (SLEDAI-2K) for SLE patients.ResultsThe RA patients (F:M 4:1) had a mean age of 36.8 ± 9.6 years and disease duration of 8.3 ± 1.1 years while the SLE patients (F:M 7.75:1) had a mean age of 35.6 ± 8.8 years and disease duration of 8.1 ± 0.87 years. There was a highly significant increase in the cf-DNA level in SLE patients (17.33 ± 2.4 ng/ml) and RA patients (11.15 ± 2.3 ng/ml) compared to the level in the control (4.15 ± 1.4 ng/ml) (p = 0.0005). The cf-DNA significantly correlated with the erythrocyte sedimentation rate (ESR) (p = 0.04), C-reactive protein (p = 0.04) and the DAS28 (p = 0.005) in the RA patients and with the ESR (p = 0.03), anti-ds-DNA (p = 0.008), complement-4 (p = 0.04) and SLEDAI-2K (p = 0.002).ConclusionThe increased cf-DNA implicates a possible role in the pathogenesis of both RA and SLE and appears to be a useful marker of disease activity in addition to other laboratory tests.