Current data suggest that aristolochic acid (AA) exposure is a putative cause of Balkan endemic nephropathy (BEN), a chronic kidney disease strongly associated with upper tract urothelial carcinoma. The cellular metabolism of AA is associated with the production of reactive oxygen species, resulting in oxidative distress. Purpose: Therefore, the aim of this study was to analyze individual, combined and cumulative effect of antioxidant gene polymorphisms (Nrf2 rs6721961, KEAP1 rs1048290, GSTP1AB rs1695, GSTP1CD rs1138272, GPX3 rs8177412 and MDR1 rs1045642), as well as GSTP1ABCD haplotypes with the risk for BEN development and associated urothelial cell carcinoma in 209 BEN patients and 140 controls from endemic areas. Experimental method: Genotyping was performed using polymerase chain reaction (PCR) and PCR with confronting two-pair primers (PCR-CTTP) methods. Results: We found that female patients carrying both variant GPX3 rs8177412 and MDR1 rs1045642 genotypes in combination exhibited significant risk towards BEN (OR 1 = 3.34, 95% CI = 1.16–9.60, p = 0.025; OR 2 = 3.79, 95% CI = 1.27–11.24, p = 0.016). Moreover, significant association was determined between GPX3rs8174412 polymorphism and risk for urothelial carcinoma. Carriers of variant GPX3*TC + CC genotype were at eight-fold increased risk of BEN-associated urothelial tumors development. There was no individual or combined impact on BEN development and BEN-associated tumors among all examined polymorphisms. The haplotype consisting of variant alleles for both polymorphisms G and T was associated with 1.6-fold increased risk although statistically insignificant (OR = 1.64; 95% CI = 0.75–3.58; p = 0.21). Conclusions: Regarding GPX3 rs8177412 polymorphism, the gene variant that confers lower expression is associated with significant increase in upper urothelial carcinoma risk. Therefore, BEN patients carrying variant GPX3 genotype should be more frequently monitored for possible upper tract urothelial carcinoma development.

Background: Among many genes which have been analyzed to understand obesity and related metabolic traits among children and adolescents, not many studies are conducted on LGALS3 gene, especially in population of children. A positive correlation of circulating galectin 3 serum levels with impaired blood glucose, high blood pressure and higher values of serum lipids and was found in general population. The aim was to investigate possible association of rs4644 with body mass index, glycaemia, and lipid profile in Serbian adolescents. Methods: The study included 72 boys and 79 girls, 14-15 years of age. Among boys 51 (67.1%) had normal values of BMI, 11 (14.5%) were overweight, and 14 (18.4%) were obese. Among girls, 53 (63.9%) had normal BMI, 16 (19.3%) were overweight, and 14 (16.9%) were obese. Diabetes type 1 or 2, genetic syndromes, generalized inflammation, cardiovascular and malignant diseases were criteria for exclusion. Genotyping was performed by Real time PCR. Results: Girls carriers of CC genotype had statistically higher mean values of BMI, and triglycerides in comparison to the girls carriers of CA+AA genotypes, p=0.041, and p=0.045, respectively. The higher frequency of obese was found among group of girls who were carriers of CC genotype, p=0.049. No statistically significant association was observed among other analyzed parameters in neither examined groups. Results: Our research indicates that there is an association between the CC genotype of rs4644 polymorphism with obesity and higher triglycerides level in the group of female adolescents.

PPARGC1A is involved in many metabolic processes including normal mitochondrial biogenesis, oxidation of glucose and lipids and transport of glucose into skeletal muscles. Previous researches linked this polymorphism with the higher risk of developing type 2 diabetes, metabolic syndrome and obesity. The aim of the study was to investigate the association of Gly482Ser with body mass index (BMI), fasting glucose levels and lipid profile in Serbian adolescents. The study included 147 boys and 150 girls, 15 years of age. Anthropometric and biochemical parameters were recorded. Cardiovascular and malignant diseases, type 2 diabetes, cerebral palsy and genetics syndrome were criteria for exclusion. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (RFLP) assay. The results showed that boys carriers of GG genotype had statistically higher mean values of TC compared to the boys who were carriers of GA+AA genotypes (p=0.033). However, statistical significance was not obtained for the other analyzed parameters. Furthermore, in the group of overweight and obese children, higher mean values of TC and LDL-C were observed in the carriers of GG genotype compared to carriers of GA+AA genotype for all the adolescents, as well as in the group of girls. No correlation was observed for values of BMI, fasting blood glucose and levels of triglycerides. To confirm these results, further research with larger sample size and non-genetics factor taking into consideration, would be of great interest.

Background/Aim: Warfarin is one of the most common orally prescribed anticoagulant in patients with deep venous thrombosis, myocardial or cerebral infarctions. The main side effects of non-adequate dose of these drugs are prolonged peripheral or internal bleeding. VKORC1 1173C>T polymorphism (rs9934438) is of particular importance, since carriers of non-wild type allele correlates with the lower dosage of warfarin therapy. Thus, the aim of the research was to determine the distribution of 1173C>T polymorphism in population of the Republic of Srpska, Bosnia and Herzegovina (RS) and to compare results with frequencies in other populations. Methods: A total of 124 healthy participants of both genders were enrolled in the study, from all parts of the RS. Molecular genotyping was performed by real-time PCR, using drug metabolism assays according to the manufacturer's instructions. Results: Of the total number, 22 subjects (17.74 %) were genotyped as CC, 69 subjects (55.65 %) as CT and 33 subjects (26.61 %) as TT. The frequencies of alleles C and T were 45.18 % and 54.82 %, respectively. No statistical significance was found among allele distribution between genders (ch² = 0.236; p = 0.627). All observed genotype frequencies were in Hardy-Weinberg equilibrium. No statistical significance was observed among the frequency of minor T allele between presented findings and other European countries, besides Russia (p = 0.021). Conclusion: This was the first study analysing the distribution of rs9934438 alleles in population of the RS. These findings will be helpful in better and more precise drug prescribing in patients who require anticoagulant therapy.