Aim: To study correlation of IgE level and C-reactive protein (CRP) for exacerbation of the disease in asthmatic patients. Methods: Asthmatic subject were examined for achieving of asthma control according to GINA recommendation. Numbers of exacerbation of asthma during one month were analyzed. The patients were followed in six month period (since first January to 30th of Jun. Average monthly days of exacerbations was calculated. IgE level in the blood was measured using Enzyme-linked Immunoassay (ELISA), and CRP was measured by immunotubidimetry. Assessment of asthma control was considered using Asthma Quality of Life Questionnaire (AQLQ). Results: The study includes 63 patients with asthma. Average level of IgE was 674 IU/mL (SD 167), range 56-3785 IU/mL, 1 IU=3,2 ng; average level of CRP was 16,4 mg/mL (SD 6,3), range 5-48; Average number of days in exacerbation during one month was 3,6 (SD 2,4), and varied from zero, patients with no exacerbation, to 21. Using test of multiple correlation it was shown statistical significant correlation (level p Conclusion: In this study CRP was shown as stronger predictor of asthma exacerbation and worse quality of life than total IgE level in asthmatic subjects.

AIM Lipin 1 is a recently discovered multifunctional protein involved in the metabolism of lipids, while PPARgamma is involved in adipocyte differentiation, and regulation of lipid metabolism. Up to now, LPIN1 and PPARG gene polymorphisms have been associated with type 2 diabetes, metabolic syndrome, and central obesity. In this study, we hypothesized that genetic variants within LPIN1 and PPARG genes were associated with traits of metabolic syndrome. Correlation between biochemical parameters (including but not limited to, glucose, HbA1c, insulin levels, HDL and LDL cholesterol, triglycerides, serum proteins, liver enzymes) and frequency of polymorphisms in LPIN1 (rs11693809 and rs2716610) and PPARG gene (rs10865710, rs3856806 and rs1801282), was tested in this study. METHODS The study included 70 patients diagnosed with metabolic syndrome and type 2 diabetes. Two polymorphisms of LPIN1 gene (rs11693809 and rs2716610), and three polymorphisms of PPARG gene (rs10865710, rs385806 and rs1801282) were analyzed by real time PCR and conventional PCR-RFLP methods. RESULTS Our analysis revealed correlation between insulin levels and rs11693809 LPIN1 polymorphism in diabetic patients. Also the results of this study showed an association of rs10865710 and rs385806 polymorphism of PPARG with HDL cholesterol and LDL plus total cholesterol levels, respectively. CONCLUSION These data reflect an association of analyzed PPARG and LPIN1 gene polymorphisms with values of insulin, HDL, LDL and total cholesterol witch indicates an important role of these genes in lipid metabolism and pathogenesis of type 2 diabetes and metabolic syndrome.

AIM To analyze usefulness of measurement amino-terminal pro-B type natriuretic peptide of (NT pro-BNP) as the one of parameters of water overload in patients with chronic kidney diseases. METHODS A total number of 277 patients with chronic kidney diseases (CKD) were followed up in the period often years between January 2000 and July 2010. Patients with creatinine clearance of 60 ml/min or less were included in the study. Changes of creatinine clearance, and in last five years changes of NT pro-BNP were followed. Water overload was analyzed using chest x-ray in relation with concentration of NT pro-BNP in the blood. RESULTS Decrease of clearance of creatinine ranged from average 54.7 ml/min in the first year to 14.6 ml/min in the fifth year of the monitoring. Average NT pro-BNP level in patients without any sign of water overload was 94 pg/ml (SD 21), mean value in those with Kerley lines was 231 pg/ml/L (SD 64), in those with clear signs of water overload but without pleural effusion it was 525 pg/ml (SD 223), and in those with water retention including pleural effusion it was 1606 pg/ml (SD 1134). Using test of multiple correlation a statistically significant correlation between X-ray signs of water overload and NT pro-BNP concentration was shown, p < 0.05. CONCLUSION Measurement of NT pro-BNP was increased in the beginning of water overload in patients with CKD. Increased value of NT pro-BNP may be found earlier than any other signs of water overload. NT pro-BNP was a useful parameter in estimation of water overload in these patients.

AIM Differences in the frequency of distribution of the cytochrome P450 (CYP) allelic variants have been demonstrated between distinct ethnic groups, contributing to observed interindividual variation in drug response. In this study we determined, for the first time, prevalence of the common allelic variants of the polymorphic CYP enzymes, CYP3A4*1B and CYP3A5*3, in the population of Bosnia and Herzegovina (BH). METHODS Genomic DNA was extracted from blood samples collected from 140 unrelated subjects. A real-time PCR was used for the detection of CYP polymorphisms, with the application of the specific TaqMan SNP Genotyping Assay (Applied Biosystems) for CYP3A5*3, while CYP3A4*1B was genotyped by high-resolution melting analysis. RESULTS Our results have shown that the distribution of CYP3A4*1B and CYP3A5*3 alleles was in line with the data reported in European Caucasians. We confirmed that CYP3A4*1B mutant allele is rare in Caucasians, being present in only 5.1% individuals. However, CYP3A5*3 polymorphism was found to be predominant in the Bosnian population with an incidence of 94%, similarly to other European populations tested so far. Interestingly, we have demonstrated a strong linkage disequilibrium between CYP3A5*3 and CYP3A4*1B alleles. No significant difference in allele frequencies for CYP3A4*1B and CYP3A5*3 has been shown between male and female subjects participating in our study. CONCLUSION Our data demonstrated the high prevalence of CYP3A5*3 allele in Bosnian population, indicating significance of analysis of CYP3A5 and CYP3A4 polymorphisms and corresponding allele frequencies in specific ethnic groups. Importantly, results of this study may lead to translation of pharmacogenetics and individualized therapeutic approach in current clinical practices in BH.

This is the first study performed in population from Bosnia & Herzegovina (BH), in which we analysed a significance of genetic variations in drug-metabolising enzyme, cytochrome P450 (CYP), in pathogenesis of Type 2 diabetes. We have determined allele frequencies for CYP2C9*2, CYP2C19*2, and CYP2D6*4 in diabetic patients and nondiabetic controls. Genomic DNA was extracted from blood samples collected from 37 diabetic and 44 nondiabetic subjects. A real-time polymerase chain reaction was used for the detection of specific CYP polymorphisms, with the application of the specific TaqMan® SNP genotyping tests (Applied Biosystems). Interestingly, results from this study have demonstrated that frequencies of CYP2C19*2 and CYP2D6*4 variants were in line, while frequency of CYP2C9*2 polymorphism seemed to be lower in this sample of BH population as compared to the Caucasians genotype data. Furthermore, no significant difference in allele frequencies for CYP2C9*2, CYP2C19*2, and CYP2D6*4 was demonstrated between diabetic and nondiabetic subjects. Thus, results form this study seem to indicate no relationship between CYP2C9, CYP2C19, and CYP2D6 genotype and diabetes susceptibility in Bosnian population. This in part may reflect a limited study population included in our study and would require larger cohorts to reveal potential relationships between analysed CYP genetic variants and diabetes risk. In addition, it would be pertinent to further explore possible effects of CYP genetic variations on therapeutic and adverse outcomes of oral antidiabetics, which might be the key in optimising therapy for individual patient with Type 2 diabetes.

Recent studies have introduced serum uric acid (UA) as a potential risk factor for developing diabetes, hypertension, stroke, and cardiovascular diseases. The value of elevated levels of UA in serum as a risk factor for diabetes development is still under scrutiny. Recent data suggest that clearance of UA is being reduced with increase in insulin resistance and UA as a marker of prediabetes period. However, conflicting data related to UA in serum of patients with Type 2 diabetes prompted us to study the urine/serum ratio of UA levels (USRUA) in these patients and healthy controls. All subjects included in the study were free of evidence of hepatitis B or C viral infection or active liver and kidney damage. Patients receiving drugs known to influence UA levels were also excluded from this study. Analysis of glucose and uric acid were performed on Dade Behring analyzer using standard IFCC protocols. Interestingly, our data demonstrated about 2.5 fold higher USRUA values in diabetic patients as compared to control subjects. Furthermore, there was a trend of correlation of USRUA value with the blood glucose levels in diabetic patients, which was more prominent in diabetic men than in women. With aging, levels of uric acid increased in serum of diabetic patients, and this effect was also more profound in male than in female diabetics. In conclusion, this study showed significantly elevated USRUA levels in patients with Type 2 diabetes, a negative USRUA correlation with the blood glucose levels in diabetic patients, and an effect of sex and age on the uric acid levels. Since literature data suggest a strong genetic effect on UA levels, it would be pertinent to perform further, possibly genetic studies, in order to clarify gender and ethnic differences in UA concentrations.

Th is is the fi rst study performed in population from Bosnia & Herzegovina (BH), in which we analysed a signifi cance of genetic variations in drug-metabolising enzyme, cytochrome P (CYP), in pathogenesis of Type  diabetes. We have determined allele frequencies for CYPC*, CYPC*, and CYPD* in diabetic patients and nondiabetic controls. Genomic DNA was extracted from blood samples collected from  diabetic and  nondiabetic subjects. A real-time polymerase chain reaction was used for the detection of specifi c CYP polymorphisms, with the application of the specifi c TaqMan® SNP genotyping tests (Applied Biosystems). Interestingly, results from this study have demonstrated that frequencies of CYPC* and CYPD* variants were in line, while frequency of CYPC* polymorphism seemed to be lower in this sample of BH population as compared to the Caucasians genotype data. Furthermore, no signifi cant diff erence in allele frequencies for CYPC*, CYPC*, and CYPD* was demonstrated between diabetic and nondiabetic subjects. Th us, results form this study seem to indicate no relationship between CYPC, CYPC, and CYPD genotype and diabetes susceptibility in Bosnian population. Th is in part may refl ect a limited study population included in our study and would require larger cohorts to reveal potential relationships between analysed CYP genetic variants and diabetes risk. In addition, it would be pertinent to further explore possible eff ects of CYP genetic variations on therapeutic and adverse outcomes of oral antidiabetics, which might be the key in optimising therapy for individual patient with Type  diabetes. ©  Association of Basic Medical Sciences of FBIH. All rights reserved