Methylene tetrahydrofolate reductase, transforming growth factor-β1 and lymphotoxin-α genes polymorphisms and susceptibility to rheumatoid arthritis

AbstractBackgroundRheumatoid arthritis is a widely prevalent autoimmune disorder with suggested genetic predisposition.ObjectivesThe aim of this study is to detect the pattern of genetic polymorphism of methylene tetrahydrofolate reductase (MTHFR C677 T and A1298 C), transforming growth factor-β1 (TGF-β1 T869 C) and lymphotoxin-α (LT-α A252G) in patients having rheumatoid arthritis and correlate these patterns to disease activity and serum levels of tumor necrosis factor-alpha (TNF-α), B-Cell Activating Factor (BAFF), and osteopontin.MethodsA total of 194 subjects, 90 controls and 104 patients with rheumatoid arthritis were genotyped for MTHFR C677 T and A1298 C, TGF-β1 T869 C and LT-α A252G polymorphisms using a methodology based on PCR-RFLP. Also serum levels of TNF-α, osteopontin and BAFF were measured by ELISA kits.ResultsThe CT genotype and T allele of MTHFR C677 T and GG genotype and G allele of LT-α A252G are associated with the risk of RA and with higher levels of the pro-inflammatory cytokine, TNF-α in patients with rheumatoid arthritis.ConclusionOur findings suggest that there is association between MTHFR C677 T and LT-α A252G genes polymorphisms and increased risk of RA in this sample of Egyptian population

Polimorfismos dos genes metilenotetrahidrofolato redutase, fator de crescimento transformador β1 e linfotoxina‐α e susceptibilidade à artrite reumatoide

ResumoAntecedentesA artrite reumatoide é uma doença autoimune amplamente prevalente com sugerida predisposição genética.ObjetivosDetectar o padrão de polimorfismo dos genes metilenotetrahidrofolato redutase (MTHFR C677T e A1298C), fator de crescimento transformador β1 (TGF‐β1 T869C) e linfotoxina‐α (LT‐α A252G) em pacientes com artrite reumatoide e correlacionar esses padrões com a atividade da doença e os níveis séricos de fator de necrose tumoral alfa (TNF‐α), fator ativador de linfócitos B (BAFF) e osteopontina.MétodosForam genotipados 194 indivíduos – 90 controles e 104 com artrite reumatoide – à procura de polimorfismos dos genes MTHFR C677T e A1298C, TGF‐β1 T869C e LT‐α A252G com uma metodologia baseada na PCR‐RFLP. Mensuraram‐se também os níveis séricos de TNF‐α, osteopontina e BAFF com kits de Elisa.ResultadosO genótipo CT e o alelo T do MTHFR C677T e o genótipo GG e alelo G do LT‐α A252G estão associados ao risco de AR e a níveis mais elevados da citocina pró‐inflamatória TNF‐α em pacientes com artrite reumatoide.ConclusãoOs achados do presente estudo sugerem que há associação entre os polimorfismos dos genes MTHFR C677T e LT‐α A252G e um risco aumentado de AR nessa amostra da população egípcia.AbstractBackgroundRheumatoid arthritis is a widely prevalent autoimmune disorder with suggested genetic predisposition.ObjectivesThe aim of this study is to detect the pattern of genetic polymorphism of methylene tetrahydrofolate reductase (MTHFR C677T and A1298C), transforming growth factor‐β1 (TGF‐β1 T869C) and lymphotoxin‐α (LT‐α A252G) in patients having rheumatoid arthritis and correlate these patterns to disease activity and serum levels of tumor necrosis factor‐alpha (TNF‐α), B‐Cell Activating Factor (BAFF), and osteopontin.MethodsA total of 194 subjects, 90 controls and 104 patients with rheumatoid arthritis were genotyped for MTHFR C677T and A1298C, TGF‐β1 T869C and LT‐α A252G polymorphisms using a methodology based on PCR‐RFLP. Also serum levels of TNF‐α, osteopontin and BAFF were measured by ELISA kits.ResultsThe CT genotype and T allele of MTHFR C677T and GG genotype and G allele of LT‐α A252G are associated with the risk of RA and with higher levels of the pro‐inflammatory cytokine, TNF‐α in patients with rheumatoid arthritis.ConclusionOur findings suggest that there is association between MTHFR C677T and LT‐α A252G genes polymorphisms and increased risk of RA in this sample of Egyptian population

Significance of hepatocyte growth factor concentrations in serum of patients with liver cirrhosis and patients with hepatocellular carcinoma

Objective Egypt has the highest prevalence of chronic hepatitis C virus (HCV) infection worldwide with the development of cirrhosis and hepatocellular carcinoma (HCC). The hepatocyte growth factor (HGF)-cMET axis promotes cell survival, proliferation, migration, and invasion. This study aimed to evaluate the role of serum HGF as a noninvasive biomarker in the diagnosis of liver cirrhosis and HCC. Patients and methods This study included 80 individuals. They were divided into three groups: group 1 included 20 healthy volunteers as a control group, group 2 included 30 patients with liver cirrhosis, and group 3 included 30 patients with HCC. Results HGF was highly significantly elevated in the HCC group (median 3709 pg/ml) and the cirrhotic group (median 2843.5 pg/ml) compared with the control group (median 913 pg/ml). α-Fetoprotein (AFP) was highly significantly elevated in the HCC group (median 128.5 ng/ml) than both the cirrhotic (median 4.9 ng/ml) and the control (median 3.15 ng/ml) group. Results of aspartate aminotransferase/alanine aminotransferase, APRI, fibroindex, and model 3 in the cirrhotic group were highly significantly different from those in the control group. We found a positive significant correlation between HGF and AFP for all the participants studied. There were direct correlations between HGF and aspartate aminotransferase/platelet ratio index (APRI), fibroindex, and model 3. The sensitivity and specificity of HGF for selective detection of the HCC group over the non-HCC group (HCV group and healthy control group) were 93.3 and 46%, respectively, at a cut-off value of 1415 pg/ml, whereas that of AFP were 100 and 92%, respectively, at a cut-off value of 10 ng/ml, and area under the curve of HGF and AFP were 0.787 and 0.999, respectively. The sensitivity and specificity of both AFP and HGF together were 100 and 66%, respectively, at the same cut-off values. The odds ratio of occurrence of HCC in patients with elevated HGF levels was 11.926 and 95% confidence interval 2.56-55.55. Conclusion We conclude from this study that both HGF and AFP can be used as noninvasive biomarkers for early detection of HCC in HCV cirrhotic patients, especially if their values match the cut-off levels detected in our study

Seroprevalence and real-time PCR study of Epstein-Barr virus and the value of screening in pretransplant patients

Objective This study was performed to estimate the prevalence of Epstein-Barr virus immunoglobulin M virus capsid antigen (EBV IgM VCA) among healthy blood donors and to confirm the real risk of transfusion transmission by detection of virus load using PCR quantification. Materials and methods A total of 860 apparently healthy Egyptian blood donors were enrolled and tested for EBV IgM VCA. Quantitative PCR was performed for reactive cases for EBV IgM VCA. Results An overall 38 patients were reactive for EBV IgM VCA, constituting 4.4% of the sample. Reactivity of Epstein-Barr virus did not differ significantly as regards sex distribution, blood grouping, Rh factor positivity, and hemoglobin level, but it was significantly higher among upper Egypt participants than among those from other regions (P = 0.006). There was a very high statistically significant positive correlation between the titer of EBV VCA IgM reactive cases and age in the studied group (P = 0.0001 and r = 0.6). PCR was negative for all of the reactive cases. Conclusion Routine screening for Epstein-Barr virus in blood bags is not economical. Screening is highly recommended only for immunocompromised and pretransplant patients. Viremia is not the role in individuals with EBV IgM positive sera, which in turn changes some concepts in organ transplantation

Methylene tetrahydrofolate reductase, transforming growth factor-β1 and lymphotoxin-α genes polymorphisms and susceptibility to rheumatoid arthritis

ABSTRACT Background: Rheumatoid arthritis is a widely prevalent autoimmune disorder with suggested genetic predisposition. Objectives: The aim of this study is to detect the pattern of genetic polymorphism of methylene tetrahydrofolate reductase (MTHFR C677 T and A1298 C), transforming growth factor-β1 (TGF-β1 T869 C) and lymphotoxin-α (LT-α A252G) in patients having rheumatoid arthritis and correlate these patterns to disease activity and serum levels of tumor necrosis factor-alpha (TNF-α), B-Cell Activating Factor (BAFF), and osteopontin. Methods: A total of 194 subjects, 90 controls and 104 patients with rheumatoid arthritis were genotyped for MTHFR C677 T and A1298 C, TGF-β1 T869 C and LT-α A252G polymorphisms using a methodology based on PCR-RFLP. Also serum levels of TNF-α, osteopontin and BAFF were measured by ELISA kits. Results: The CT genotype and T allele of MTHFR C677 T and GG genotype and G allele of LT-α A252G are associated with the risk of RA and with higher levels of the pro-inflammatory cytokine, TNF-α in patients with rheumatoid arthritis. Conclusion: Our findings suggest that there is association between MTHFR C677 T and LT-α A252G genes polymorphisms and increased risk of RA in this sample of Egyptian population