Browsing by Author "Majkić-Singh, Nada (56254156200)"

The primary role of alpha-1-antitrypsin (AAT), encoded by the highly polymorphic SERPINA1 gene, is to protect the lung parenchyma from proteolysis by neutrophil elastase. AAT deficiency (AATD) is an autosomal recessive disease, considered as the most important genetic cause of liver disease in children and emphysema in adults. According to frequency, deficient alleles can be classified as common (Z and S) and rare (Mmalton, Mheerlen, Mprocida etc). Type, intensity and onset of clinical disease associated with AATD occur as a result of interaction between AATD and additional genetic and acquired factors (tobacco smoking, air pollution exposure etc). The most frequent clinical manifestations include premature emphysema, chronic hepatitis, cirrhosis and hepatocellular carcinoma. Epidemiological studies highlight the need for improvement in diagnostic efficiency for AATD. It is recommended for a diagnostic approach to integrate precise, internationally recognized clinical criteria and a standardized laboratory protocol, based on a combination of biochemical and molecular methods. The predilection site of clinical manifestations guides the therapeutic approach. Augmentation therapy is possible in lung disease, while currently the only specific measure in patients with severe liver failure due to AATD is transplantation. In all patients, preventive measures, ammeliorating the deleterious effects of habits and environmental factors are recommended. Introduction of gene therapy is expected to additionally improve health outcomes in affected persons. Current results with an integrative AATD diagnostic strategy in the Serbian population are highly encouraging, prompting towards its further implementation in common medical practice with the ultimate goal to establish a national register of affected individuals.

The primary role of alpha-1-antitrypsin (AAT), encoded by the highly polymorphic SERPINA1 gene, is to protect the lung parenchyma from proteolysis by neutrophil elastase. AAT deficiency (AATD) is an autosomal recessive disease, considered as the most important genetic cause of liver disease in children and emphysema in adults. According to frequency, deficient alleles can be classified as common (Z and S) and rare (Mmalton, Mheerlen, Mprocida etc). Type, intensity and onset of clinical disease associated with AATD occur as a result of interaction between AATD and additional genetic and acquired factors (tobacco smoking, air pollution exposure etc). The most frequent clinical manifestations include premature emphysema, chronic hepatitis, cirrhosis and hepatocellular carcinoma. Epidemiological studies highlight the need for improvement in diagnostic efficiency for AATD. It is recommended for a diagnostic approach to integrate precise, internationally recognized clinical criteria and a standardized laboratory protocol, based on a combination of biochemical and molecular methods. The predilection site of clinical manifestations guides the therapeutic approach. Augmentation therapy is possible in lung disease, while currently the only specific measure in patients with severe liver failure due to AATD is transplantation. In all patients, preventive measures, ammeliorating the deleterious effects of habits and environmental factors are recommended. Introduction of gene therapy is expected to additionally improve health outcomes in affected persons. Current results with an integrative AATD diagnostic strategy in the Serbian population are highly encouraging, prompting towards its further implementation in common medical practice with the ultimate goal to establish a national register of affected individuals.

Background/Aim. Preeclampsia (PE) belongs to the group of hypertensive disorders in pregnancy with the global average incidence of 2.16%. It is considered as one of the leading causes of maternal and neonatal morbidity and mortality worldwide. The goal of this study was to assess the potential association between Val158Met catechol-o-methyltransferase (COMT), tumor necrosis factor-alpha (TNF-α) -857 C>T, tumor necrosis factor receptor 1 (TNFR1) 36 A>G, interleukin-1alpha (IL-1α) 4845 G>T and interleukin-10 (IL-10) -1082 A>G polymorphisms and risk of early-onset preeclampsia (PE) and its complications. Methods. The study included 47 early-onset PE patients, which were grouped by disease severity and by size for gestational age and 47 control cases. The Val158Met polymorphism was genotyped by polymerase chain reaction – restriction fragment length polymorphism (PCR-RFLP) analysis and inflammatory cytokine polymorphisms by the Sanger sequencing method. Results. The COMT Met allele as well as IL-1α T showed a protective role, decreasing the risk of early-onset PE after age and body mass index (BMI) adjustments. The detected interactions between the COMT Met and IL-10 A alleles, as well as between the COMT Met and TNF-α T alleles were insignificant after age and BMI adjustments. Conclusion. COMT and IL-1α may be used as candidate genes for early-onset PE and its severe form and small for gestational age (SGA) complications. © 2017, Inst. Sci. inf., Univ. Defence in Belgrade. All Rights Reserved.

Hyperhomocysteinemia (HHcy) is considered one of the factors related to premature atherothrombosis. Study compares incidences of HHcy, defined as homocysteinemia above 12 μmol/L, and medians of homocysteinemia between the groups of 212 patients with acute myocardial infarction (AMI) younger than 45 years of age and 45 age-matched healthy persons. Homocysteine was determined by a HPLC method with fluorescent detection. Results were compared by chi-square, Mann-Whitney U and Kruskal-Wallis tests. Significant difference (p=0.001) was observed between incidence of HHcy in patients (44.8%) and incidence in controls (17.8%). Medians of homocysteinemia levels in patients (11.4 μmol/L) and controls (9.7 μmol/L) were significantly different (p=0.001). Gender-specific differences in incidence of HHcy and in median homocysteinemia value in patients were not significant. Incidences of HHcy in female patients (47.1%) and in healthy women (4.8%) were significantly different (p=0.001). Comparison of median homocysteinemia levels in women with AMI (10.9 μmol/L) and in female controls (9.0 μmol/L) revealed significant difference (p=0.025). Such differences were not observed in male subjects of our study. No significant difference was found when incidences of HHcy and medians of homocysteinemia were compared between defined age groups of patients. We conclude that young patients with AMI have higher incidence of hyperhomocysteinemia and higher level of homocysteinemia than healthy persons. Young women with AMI have higher incidence of hyperhomocysteinemia and higher level of homocysteine than healthy young women.

Hyperhomocysteinemia (HHcy) is considered one of the factors related to premature atherothrombosis. Study compares incidences of HHcy, defined as homocysteinemia above 12 μmol/L, and medians of homocysteinemia between the groups of 212 patients with acute myocardial infarction (AMI) younger than 45 years of age and 45 age-matched healthy persons. Homocysteine was determined by a HPLC method with fluorescent detection. Results were compared by chi-square, Mann-Whitney U and Kruskal-Wallis tests. Significant difference (p=0.001) was observed between incidence of HHcy in patients (44.8%) and incidence in controls (17.8%). Medians of homocysteinemia levels in patients (11.4 μmol/L) and controls (9.7 μmol/L) were significantly different (p=0.001). Gender-specific differences in incidence of HHcy and in median homocysteinemia value in patients were not significant. Incidences of HHcy in female patients (47.1%) and in healthy women (4.8%) were significantly different (p=0.001). Comparison of median homocysteinemia levels in women with AMI (10.9 μmol/L) and in female controls (9.0 μmol/L) revealed significant difference (p=0.025). Such differences were not observed in male subjects of our study. No significant difference was found when incidences of HHcy and medians of homocysteinemia were compared between defined age groups of patients. We conclude that young patients with AMI have higher incidence of hyperhomocysteinemia and higher level of homocysteinemia than healthy persons. Young women with AMI have higher incidence of hyperhomocysteinemia and higher level of homocysteine than healthy young women.

Hyperhomocysteinemia is considered an independent risk factor for premature cardiovascular disease. Mutation MTHFR C677T reduces the activity of methylenetetra-hydrofolatereductase and may cause hyperhomocysteinemia. Incidence of hyperhomocysteinemia (homocysteine above 12 μmol/L), homocysteine level, and distribution of MTHFR C677T genotypes (C/C, C/T and T/T) are compared between young patients with acute myocardial infarction and healthy persons, matched by age. Study involved 86 patients younger than 45 years (77 men and 9 women) and 35 controls. Homocysteine was measured by an HPLC method and the MTHFR C677T genotype determined using PCR amplification and digestion with Hinf I. Statistical analyses included chisquare and Mann-Whitney U tests. Hyperhomocysteinemia was present in 32.6% patients and 14.3% controls, revealing a significant difference (P= 0.038). Median homocysteine levels in patients (10.4 μmol/L) and controls (9.6 μmol/L) were significantly different (P=0.035). Among patients, 50.0% had C/C, 41.9% C/T and 8.1% T/T genotype, and the genotype had no influence on hyperhomocysteinemia incidence and homocysteine level. Genotype distribution in patients was not significantly different from that observed in controls. The conclusion is that young patients with acute myocardial infarction have higher incidence of hyperhomocysteinemia and higher homocysteine levels than healthy young adults, while there is no significant difference in the distribution of MTHFR C677T genotypes.

Hyperhomocysteinemia is considered an independent risk factor for premature cardiovascular disease. Mutation MTHFR C677T reduces the activity of methylenetetra-hydrofolatereductase and may cause hyperhomocysteinemia. Incidence of hyperhomocysteinemia (homocysteine above 12 μmol/L), homocysteine level, and distribution of MTHFR C677T genotypes (C/C, C/T and T/T) are compared between young patients with acute myocardial infarction and healthy persons, matched by age. Study involved 86 patients younger than 45 years (77 men and 9 women) and 35 controls. Homocysteine was measured by an HPLC method and the MTHFR C677T genotype determined using PCR amplification and digestion with Hinf I. Statistical analyses included chisquare and Mann-Whitney U tests. Hyperhomocysteinemia was present in 32.6% patients and 14.3% controls, revealing a significant difference (P= 0.038). Median homocysteine levels in patients (10.4 μmol/L) and controls (9.6 μmol/L) were significantly different (P=0.035). Among patients, 50.0% had C/C, 41.9% C/T and 8.1% T/T genotype, and the genotype had no influence on hyperhomocysteinemia incidence and homocysteine level. Genotype distribution in patients was not significantly different from that observed in controls. The conclusion is that young patients with acute myocardial infarction have higher incidence of hyperhomocysteinemia and higher homocysteine levels than healthy young adults, while there is no significant difference in the distribution of MTHFR C677T genotypes.

Background: Up until now there have been contradictory data about the association between p.Val158Met catechol-O-methyltransferase (COMT) polymorphism and risk of preeclampsia (PE). The goal of this study was to assess the potential correlation between p.Val158Met COMT polymorphism and risk of early-onset PE, risk of a severe form of early-onset PE, as well as risk of small-for-gestationalage (SGA) complicating PE. Methods: The study included 47 early-onset PE patients and 47 control cases. Forty-seven early-onset PE patients were grouped by disease severity (33 patients with a severe form and 14 patients without severe features) and secondly by size for gestational age (12 patients with appropriate-for-gestational-age (AGA) and 35 patients with SGA size). p.Val158Met polymorphism was genotyped by PCR-RFLP analysis. Results: Allele analysis showed significant difference in COMT allele distribution between early-onset PE and control group as well as early-onset PE SGA and controls (p=0.04057 and p=0.0411 respectively). A statistically significant distribution difference between the severe form and form without severe features of early-onset PE patients was not observed (p>0.05). The highest difference observed was in the allele recessive model where COMT MetMet genotype was associated with decreased risk of early-onset PE (OR=0.281; 95%CI=0.092-0.7836) and PE complications including severe early-onset PE (OR= 0.304; 95%CI=0.086-0.944) and SGA early-onset PE (OR=0.284; 95%CI=0.081-0.874). Conclusions: COMT may be used as a candidate gene for early-onset PE and its severe form and SGA complications. © by Tijana Krnjeta 2016.

Background: Up until now there have been contradictory data about the association between p.Val158Met catechol-O-methyltransferase (COMT) polymorphism and risk of preeclampsia (PE). The goal of this study was to assess the potential correlation between p.Val158Met COMT polymorphism and risk of early-onset PE, risk of a severe form of early-onset PE, as well as risk of small-for-gestationalage (SGA) complicating PE. Methods: The study included 47 early-onset PE patients and 47 control cases. Forty-seven early-onset PE patients were grouped by disease severity (33 patients with a severe form and 14 patients without severe features) and secondly by size for gestational age (12 patients with appropriate-for-gestational-age (AGA) and 35 patients with SGA size). p.Val158Met polymorphism was genotyped by PCR-RFLP analysis. Results: Allele analysis showed significant difference in COMT allele distribution between early-onset PE and control group as well as early-onset PE SGA and controls (p=0.04057 and p=0.0411 respectively). A statistically significant distribution difference between the severe form and form without severe features of early-onset PE patients was not observed (p>0.05). The highest difference observed was in the allele recessive model where COMT MetMet genotype was associated with decreased risk of early-onset PE (OR=0.281; 95%CI=0.092-0.7836) and PE complications including severe early-onset PE (OR= 0.304; 95%CI=0.086-0.944) and SGA early-onset PE (OR=0.284; 95%CI=0.081-0.874). Conclusions: COMT may be used as a candidate gene for early-onset PE and its severe form and SGA complications. © by Tijana Krnjeta 2016.

Background: An increased homocysteine (Hcy) concentration may represent a metabolic marker of folate and vitamin B12 deficiency, both significant public health problems. For different reasons, patients with chronic obstructive pulmonary disease (COPD) are prone to these deficiencies. The study evaluates the reliability of Hcy concentration in predicting folate or vitamin B12 deficiency in these patients. Methods: A group of 50 COPD patients (28 males/22 females, age (x¯±SD=49.0±14.5) SD = 49.0 ± 14.5) years was enrolled. A chemiluminescent microparticle immunoassay was applied for homocysteine, folate and vitamin B12 concentration. Kolmogorov-Smirnov, Mann-Whitney U and χ2 tests, Spearman's correlation and ROC analysis were included in the statistical analysis, with the level of significance set at 0.05. Results: Average (SD) concentrations of folate and vitamin B12 were 4.13 (2.16) μg/L and 463.6 (271.0) ng/L, whereas only vitamin B12 correlated with the Hcy level (P=-0.310 (R=0.029)). Gender related differences were not significant and only a borderline significant correlation between age and folate was confirmed (R=0.279 (P=0.047)). The incidence of folate and vitamin B12 deficiency differed significantly (P=0.000 and P<0.000 for folate and vitamin B12 respectively), depending on the cut-off used for classification (4.4, 6.6 and 8.0 μg/L-folate; 203 and 473 ng/L-vitamin B12). ROC analyses failed to show any significance of hyperhomocysteinemia as a predictor of folate or vitamin B12 deficiency. Conclusion: Reliability of the Hcy concentration as a biomarker of folate or vitamin B12 depletion in COPD patients is not satisfactory, so their deficiency cannot be predicted by the occurrence of HHcy.

Background: An increased homocysteine (Hcy) concentration may represent a metabolic marker of folate and vitamin B12 deficiency, both significant public health problems. For different reasons, patients with chronic obstructive pulmonary disease (COPD) are prone to these deficiencies. The study evaluates the reliability of Hcy concentration in predicting folate or vitamin B12 deficiency in these patients. Methods: A group of 50 COPD patients (28 males/22 females, age (x¯±SD=49.0±14.5) SD = 49.0 ± 14.5) years was enrolled. A chemiluminescent microparticle immunoassay was applied for homocysteine, folate and vitamin B12 concentration. Kolmogorov-Smirnov, Mann-Whitney U and χ2 tests, Spearman's correlation and ROC analysis were included in the statistical analysis, with the level of significance set at 0.05. Results: Average (SD) concentrations of folate and vitamin B12 were 4.13 (2.16) μg/L and 463.6 (271.0) ng/L, whereas only vitamin B12 correlated with the Hcy level (P=-0.310 (R=0.029)). Gender related differences were not significant and only a borderline significant correlation between age and folate was confirmed (R=0.279 (P=0.047)). The incidence of folate and vitamin B12 deficiency differed significantly (P=0.000 and P<0.000 for folate and vitamin B12 respectively), depending on the cut-off used for classification (4.4, 6.6 and 8.0 μg/L-folate; 203 and 473 ng/L-vitamin B12). ROC analyses failed to show any significance of hyperhomocysteinemia as a predictor of folate or vitamin B12 deficiency. Conclusion: Reliability of the Hcy concentration as a biomarker of folate or vitamin B12 depletion in COPD patients is not satisfactory, so their deficiency cannot be predicted by the occurrence of HHcy.