Association of PTPN22 1858C→T polymorphism, HLA-DRB1 shared epitope and autoantibodies with rheumatoid arthritis.

To assess impact of PTPN22 1858C→T polymorphism, HLA shared epitope and autoantibodies on susceptibility and severity of rheumatoid arthritis (RA). A total of 150 RA patients and 150 controls were included in the study. Anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factor isotypes (IgG, IgM and IgA) were assayed by ELISA. PTPN22 1858C→T polymorphism was performed by RFLP analysis and HLA-DRB1 genotyping by PCR-SSP analysis. Single-view, anteroposterior radiographs of the hands and feet were obtained on all RA patients. The results showed association of PTPN22 1858 T allele with RA (OR = 2.3, 95 % CI 1.5-3.5) and bone erosion (OR = 2.9, 95 % CI 1.1-7.6). The associations increased with the combination of positive autoantibodies, HLA-DRB1 SE with PTPN22 1858 T allele carriage. The highest association was with the combination with anti-CCP antibodies (OR = 47.3, 95 % CI 10.9-204.4 for RA and OR = 69.4, 95 % CI 15.8-305.5 for erosion p < 0.001). Combination of PTPN22 1858 T allele carriage with negative RF isotypes or with absence HLA-DRB1 SE showed no significant association with RA. The presence of PTPN22 1858C→T polymorphism with HLA SE and autoantibodies increases risk of RA development and erosive disease.

Significance of MiRNA-34a and MiRNA-192 as a risk factor for nonalcoholic fatty liver disease.

BACKGROUND AND AIMS: NAFLD is one of the fast-growing health problems that affects up to 25% of people worldwide. Numerous miRNAs have been clarified as important regulators of liver pathophysiology, including NAFLD. Thus, we investigated the expression of the MiRNA-34a and MiRNA-192 as diagnostic markers for NAFLD. PATIENTS AND METHODS: Blood samples were collected from NAFLD cases and healthy controls. The expression profile of both studied miRNAs was detected via real-time PCR analysis. RESULTS: The present study showed that both studied miRNAs were upregulated in NAFLD patients compared to controls. Interestingly, miRNA-34a and MiRNA-192 are upregulated in NAFLD patients with early fibrosis compared to controls [with a fold change of 4.02 ± 11.49 (P = 0.05) and 18.43 ± 47.8 (P = 0.017), respectively]. However, miRNA-34a is downregulated in NAFLD patients with advanced fibrosis compared to controls, with fold expression of 0.65 ± 1.17 (P = 0.831). The area under the receiver operating characteristics (AUROC) for miRNA-34a and miRNA-192 were 0.790 and 0.643, respectively; furthermore, the sensitivities and specificities were 76.7%, 100% for miRNA-34a and 63.3%, and 93.3% for miRNA-192 (P < 0.05). Additionally, MiRNA34a was positively correlated with hypertension and fasting blood sugar, and it also was negatively correlated with hemoglobin level and total leucocyte count (P < 0.05). CONCLUSION: The results obtained indicated that both studied miRNAs could potentially be used as diagnostic biomarkers for the early stage of liver fibrosis in NAFLD cases. Also, miRNA-34a was positively correlated with metabolic disorders associated with NAFLD such as hypertension and diabetes. However, their expression showed no association with advanced fibrosis. Thus, larger cohorts are necessitated to certify the utility of serum MiRNA-34a and MiRNA-192 in monitoring the deterioration of NAFLD.

Relationship between codon 249 mutation in exon 7 of p53 gene and diagnosis of hepatocellular carcinoma.

INTRODUCTION: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Multiple genetic and epigenetic changes are involved in the molecular pathogenesis of HCC. Heat shock proteins have essential roles in protecting cells from the potentially lethal effects of stress. Among them, HSP70 are often overexpressed in cells of various cancers and have been suggested to contribute to tumourigenesis. p53 mutations in codon 249 have also been identified in HCC. MATERIAL AND METHODS: Fifty patients with liver disease were enrolled in this study compared to 10 healthy volunteers. The studied patients were divided into 2 groups: group I includes those suffering from HCC, group II includes those suffering from post-hepatitis B and C liver cirrhosis. The presence of p53 gene mutation was detected by DNA extraction from whole blood of patients and controls followed by polymerase chain reaction then restriction fragment length polymorphism (RFLP) analysis of codon 249 of exon 7. We also studied the genotypes of the HSP70 gene by PCR followed by RFLP analysis. RESULTS: Our results revealed no statistical difference between group I, group II, and the control group as regards exon 7 mutation of the p53 gene. Also the frequency of polymorphic genotypes of HSP70 showed no significant difference between the 3 studied groups. CONCLUSIONS: The present study supports the view that the incidence of point mutation of p53 codon 249 mutations in exon 7 of the p53 gene may not play a role in carcinogenesis of HCC in Egyptian patients. Also, genetic polymorphism in HSP70 was not associated with high risk of future development of HCC.