Interaction of thrombophilic SNPs in patients with unexplained infertility-multifactor dimensionality reduction (MDR) model analysis.

PURPOSE: Our aim was to evaluate the frequency and SNP-SNP interactions between factor V Leiden (FVL) G1691A, prothrombin G20210A mutation, and C677T MTHFR and PAI-1 4G/5G gene polymorphisms in female IVF patients with unexplained infertility (UI) by using a multifactor dimensionality reduction (MDR) model analysis. METHODS: A total of 225 subjects were enrolled in the study. There were 105 females in UI group and 120 healthy controls. Designated SNPs were determined by using allele-specific PCR methods. The difference in thrombophilia prevalence was assessed by a chi-square test and logistic regression analysis. Four-locus SNP interaction model was tested using the MDR approach. A ten-fold cross-validation consistency (CVC) and permutation testing were performed. RESULTS: There was a significant difference of MTHFR C677T polymorphism frequency between the groups. Significantly less UI patients had MTHFR CC genotype (p = 0.005), while the risk allele T was more frequent (OR = 1.83, p = 0.0018). Logistic regression determined a significant association only for MTHFR C677T in our patients (TT genotype OR = 2.99). The MDR analysis confirmed the significance of a single-locus model for MTHFR C677T polymorphism (p = 0.015; OR = 2.93). However, the best, significant predictive model was the two-locus model comprising MTHFR C677T and FVL (CVC = 10/10, testing accuracy = 60.95%, p = 0.013; OR = 3.02). CONCLUSION: The MTHFR C677T polymorphism was significantly associated with UI, with minor allele T being more frequent. Additionally, there was a significantly increased presence of MTHFR C677T with FVL mutation in these patients. Therefore, MTHFR and its interaction with FVL should be recognized as contributing factors in the pathogenesis of infertility.

Hepatitis C viral infection among prisoners.

BACKGROUND/AIM: Hepatitis C virus (HCV) infection is an important sociomedical problem worldwide because the chronification of the disease is frequent and the occurance of liver cirrhosis and hepatocellular carcinoma can be expected. The aim of this study was to determine the way of infection, pathohistological changes of the liver, virus genotype presence and sustained virological response after pegylated interferon and ribavirin therapy in prison inmates. METHODS: The study included 52 patients with chronic HCV infection classified in two groups managed during 2008-2010. The first group consisted of prisoners (n = 22) and the second one of "non-prisoners" (n = 30). The patients from both groups underwent diagnostic preparation (biochemical analyses, liver biopsy, hepatitis virus detection and genotypisation using polymerase chain reaction issue). The treatment lasted for 24 weeks for virus genotypes 2 and 3, and 48 weeks for genotypes 1 and 4. RESULTS: All the patients were males, approximately the same age (35 +/- 4.1 and 31 +/- 7.6 years). Virus genotype 1 was significantly more frequent in the prisoners (p < 0.05), that demanded longer treatment (48 weeks). At the same time, statistically significant higher number of patients, "non-prisoners", achieved a sustained virological response (p < 0.01). CONCLUSION: Intravenous drug abuse and tattoos, separately or together, are the most frequent way of infection in prisoners. The dominant presence of virus genotype 1 resulted in lower number of patients with sustained virological response, probably regardless prison environment and regime.

[Side effects of antiviral therapy in patients with chronic hepatitis C infection].

INTRODUCTION: Chronic hepatitis C currently represents a global health problem, which is expected to be reduced by pegylated-interferon and ribavirin therapy. MATERIAL AND METHODS: We examined 88 patients with chronic hepatitis C, divided into three groups according to their comorbidity: the patients without comorbidity were in group I, group III included the patients on dialysis, and group III included the patients with hemophilia. RESULTS A significant difference was found in the percentage of achieved sustained virological response between the patients on dialysis and other patients, p < 0.05. Having analyzed the therapy adverse effects, we observed a significantly higher decrease of erythrocytes count, hemoglobin and hematocrit levels in dialysis patients compared to others (p < 0.01). The patients on hemodialysis predominantly had anemia and leukopenia, while thrombocytopenia was equally present in all groups. The dominant clinical side effect was flu-like syndrome, present in more than a half of patients. DISCUSSION: The therapy positive effect is usually accompanied with adverse effects. The lowest therapeutic response was recorded in group II, due to the virus genotype 1. A significant decrease in hematological parameters was determined in all patients. The most common clinical adverse effect was flu-like syndrome, later manifestations included: weight loss, alopecia, insomnia and irritability. Side effects like psychosis, thyroid gland dysfunction or psoriasis were not recorded. CONCLUSION: A significant decrease in the value of all these hematological parameters was found in all groups of patients. Clinical side effects were present in 60% of patients. Side effects did not lead to discontinuation of therapy, but only to modification of drug doses.