Potential clinical variants detected in mitochondrial DNA D-loop hypervariable region I of patients with non-alcoholic steatohepatitis.

PURPOSE: Non-alcoholic steatohepatitis (NASH) is a mitochondrial disease. However, the underlying role of mitochondrial genetics has not yet been completely elucidated. Evaluation of D-loop nucleotide variations with respect to statistical significance and clinical data distribution. METHODS: Genomic DNAs were extracted from the peripheral blood samples of patients with biopsy-proven 150 NASH as well as from 150 healthy individuals to explore the functional D-loop region responsible for the replication and transcription of the mitochondrial genome. DNA sequencing by capillary electrophoresis analysis was performed for the D-loop region of mitochondrial DNA containing the hypervariable region I, and restriction fragment length polymorphism with MnlI analysis was performed for the m.16189 T/C D-loop variant. RESULTS: The m.A16318C variant was detected only in patients with NASH and approached significance level. Based on clinical data, six variants associated with histological subgroups of NASH and NASH-complicated diseases were identified. In patients with NASH, the m.16129 AA genotype was associated with advanced-stage fibrosis; the m.16249 CC genotype was associated with advanced lobular inflammation and advanced-stage histological steatosis; the m.16296 TT genotype was associated with hypothyroidism; the m.16163 GG and m.16294 TT genotypes were associated with metabolic syndrome; and the m.16256 TT+CT genotypes were associated with type II diabetes. In patients with NASH, microRNAs were estimated by targeting the significant variants identified in this study. CONCLUSION: These findings suggest that NASH may be associated with D-loop nucleotide variations and that microRNA-based in vitro and/or in vivo studies may be developed by targeting the D-loop variants.

The role of miRNAs as a predictor of multicentricity in breast cancer.

Expression profiles of miRNAs are shown to be different in various cancers to regulate expression of mRNA or to have a role in inhibition of translation, thus it shows the possible effect in progression, invasion and metastasis of breast cancer cells. The effect of breast conserving treatment in local recurrence and survival rates for the patients who have multicentric breast cancer is still controversial. In our study, we intended to evaluate the foresight of 84 miRNAs which are identified in breast cancer for having differentiated expressions. Thirty-one patients with unifocal and 26 patients with multicentric breast cancer were included in this study. These tissue samples of both malignant and normal breast tissues were kept in RNA later solution at - 80 °C. Eighty-four miRNAs were studied with miScript miRNA PCR Array Human Breast Cancer kit. Fold change, cut off value was accepted as four. In unifocal group, there were 13 upregulated and five downregulated miRNAs and in multicentric group, there were three upregulated and seven downregulated miRNAs. To reach better results for breast cancer diagnosis and treatment, it is important to enlighten tumor biology, and pay attention to target and individual therapy. Thus, miRNAs have potential role in identifying tumor characteristics in supporting diagnosis and resulting with better evaluated disease for better treatment results with individual strategies.