The aim of the present study was to analyse effects of sulphonylurea treatment on parameters of glycaemic control in relation to transcription factor 7-like 2 (TCF7L2) genotypes. In 87 patients with type 2 diabetes who failed to achieve glycaemic control on metformin monotherapy, effects of 6-month sulphonylurea in addition to metformin on reductions in haemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) levels were evaluated. Reduction in HbA1c and FPG in response to 6-month sulphonylurea treatment was significantly higher in patients with CC genotype compared to those with the CT+TT genotype (1.16 ± 0.07 vs. 0.86 ± 0.07%, p = 0.003; 1.57 ± 0.12 vs. 1.14 ± 0.14 mmol/l, p = 0.031, respectively). In the multivariate analysis, baseline HbA1c and the TCF7L2 genotype were the only significant predictors of HbA1c reduction. In conclusion, the magnitude of HbA1c and FPG reductions after 6-month sulphonylurea treatment in addition to metformin is related to the TCF7L2 gene polymorphism.

P-glycoprotein (PGP), the product of the MDR1 gene, is a transmembrane active efflux pump for a variety of carcinogens and cytostatics. It has been suggested that MDR1 polymorphisms contribute to the variability in cancer risk and therapeutic outcome. We examined the relevance of C3435T polymorphism in relation to breast cancer susceptibility, clinical and pathological characteristics of breast carcinoma, the therapeutic response and hematologic toxicities after anthracycline-based chemotherapy. A significant association between allele frequencies and histological type, stage and histological grade was observed (P ¼ 0.024, 0.014, 0.006, respectively, w 2 -test or Fisher's exact test). We also found significantly higher (P ¼ 0.019, w 2 -test) T allele frequency in breast cancer patients (n ¼ 221) than in controls (n ¼ 113). A significantly enhanced therapeutic outcome after neoadjuvant therapy (n ¼ 38; P ¼ 0.021, Fisher's exact test) and longer time to progression after anthracycline-based chemotherapy (n ¼ 102; P ¼ 0.049, log-rank test) were observed in CC homozygotes. However, no significant association between hematologic toxicities and C3435T polymorphism was detectable.

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Aim To determine the risk of chronic obstructive pulmonary disease (COPD) associated with polymorphisms in the glutathione S-transferase (GST) M1, GST T1, and microsomal epoxide hydrolase (EPHX1) genes in a cohort of Slovak population.Methods Two hundred and seventeen patients with the diagnosis of COPD and 160 control subjects were enrolled in the study. Blood samples were collected from all subjects and the DNA from peripheral blood lymphocytes was used for subsequent genotyping assays, using polymerase chain reaction and restriction fragment-length polymorphism methods.Results In an unadjusted model, an increased risk for COPD was observed in subjects with EPHX1 His113-His113 genotype (odds ratio [OR], 2.32; 95% confidence interval [CI], 1.20-4.69; P = 0.008), compared with the carriers of the Tyr113 allele. However, after the adjustments for age, sex, and smoking status, the risk was not significant (adjusted OR, 1.79; 95% CI, 0.91-3.53; P = 0.093). In a combined analysis of gene polymorphisms, the genotype combination EPHX1 His113-His113/GSTM1 null significantly increased the risk of COPD in both, unadjusted (OR, 5.08; 95% CI, 1.70-20.43; P = 0.001) and adjusted model (OR, 4.87; 95% CI, 1.57-15.13; P = 0.006).Conclusion Although none of the tested gene polymorphisms was significantly related to an increased risk of COPD alone, our results suggest that the homozygous exon 3 mutant variant of EPHX1 gene in the combination with GSTM1 null genotype is a significant predictor of increased susceptibility to COPD in the Slovak population. The findings of the present study emphasize the importance of detoxifying and antioxidant pathways in the pathogenesis of COPD.

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