In the final phase of clot formation, fibrinogen constitutes frame, whereas factor XIII (FXIII) active form is responsible for the covalent cross-linking of fibrin fibres and plasmin inhibitor (PI), ...thus contributing to clot stability. It could be expected that any change of coagulation factors' structure affects the clot formation and modulates the atherothrombotic risk. The aim was to determine the frequency of four single nucleotide polymorphisms: (
) A > G in codon 312 of the fibrinogen α-chain gene (rs6050, Thr312AlaFGA), (
) C > T at position 10034 of the 3 - untranslated region in the fibrinogen γ-chain gene (rs2066865, 10034C > T FGG), (
) C > T in codon 564 of the FXIII-A subunit gene (rs5982, Pro564LeuFXIII-A), and (
) C > T in codon 6 of the plasmin inhibitor gene (rs2070863, Arg6TrpPI) in Croatian patients and their association with coronary artery disease (CAD).
We performed the unrelated case-control association study on the consecutive sample of patients 18 years old, who had undergone coronary angiography for investigation of chest pain and suspected CAD. The cases were patients with confirmed CAD (N=201), and the controls were the subjects with no CAD (N=119). Samples were genotyped using PCR-RFLP analysis.
Observed frequencies of the rare alleles of Thr312Ala FGA, 10034C > T FGG, Leu564Pro FXIII-A and Arg6Trp PI polymorphisms were 21%, 17%, 14%, 20%, respectively. Patients with 10034C > T FGG CC genotype had 3.5 times (95% CI 1.02-12.03) higher adjusted odds for CAD than patients with 10034C > T FGG TT genotype. Patients with Arg6Trp PI CC genotype had 3.86 times (95% CI 1.23-12.12) higher odds for CAD than patients with Arg6Trp PI TT genotype. It seems that those genotype-related higher odds are also male-gender related. No difference was observed regarding any other investigated polymorphism.
Our finding suggests that 10034C > T FGG and Arg6Trp PI are associated with CAD.
Development of nonmelanoma skin cancers (NMSCs) has been associated with certain risk factors, but studies of the association between ABO blood group and NMSCs have been rare and inconclusive. The ...aim of this study was to assess the association of the previously known risk factors and blood group as a new potential risk factor in NMSCs.
The study included 401 patients, 202 men, and 199 women, which included 367 diagnosed cases of basal cell carcinoma and 148 diagnosed cases of squamous cell carcinoma. The control group consisted of 438 subjects, 198 men, and 240 women. A standardized questionnaire adapted for this targeted study was used. The relation between the dependent variable (NMSCs) and independent variables was investigated by logistic regression.
Compared to the non AB blood group, the risk of developing NMSCs was significantly higher in the AB blood group (MOR = 2.28; 95% CI = 1.41-3.69). We established a logistic model that could best describe the probability of NMSCs development.
Study results are expected to instigate basic research into the role of A and B antigens in normal skin epithelium, NMSCs etiopathogenesis, possible effect on metastatic potential and disease prognosis, potential tumor immunotherapy, and targeted detection and prevention in subjects at an increased risk of NMSCs development.
Dioxins and human toxicity Marinkovic, Natalija; Pasalic, Daria; Ferencak, Goran ...
Arhiv za higijenu rada i toksikologiju,
12/2010, Letnik:
61, Številka:
4
Journal Article
Recenzirano
Odprti dostop
The term dioxins usually refers to polychlorinated dibenzo-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). As 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) has the highest toxic potential, ...the toxic potentials of other PCDDs and PCDFs are defined in comparison with it. Human exposure to dioxins can be environmental (background), occupational, or accidental pollution. In the human body, dioxins are in part metabolised and eliminated, and the rest is stored in body fat. People vary in their capacity to eliminate TCDD, but it is also dose-dependent; the elimination rate is much faster at higher than lower levels. The liver microsomal P4501A1 enzyme oxygenates lipophilic chemicals such as dioxins. It is encoded by the CYP1A1 gene. Cytosolic aryl hydrocarbon receptor (AhR) mediates their carcinogenic action. It binds to dioxin, translocates to nucleus and together with hydrocarbon nuclear translocator (ARNT) and xenobiotic responsive element (XRE) increases the expression of CYP1A1.Dioxins are classified as known human carcinogens, but they also cause noncancerous effects like atherosclerosis, hypertension, and diabetes. Long-term exposures to dioxins cause disruption of the nervous, immune, reproductive, and endocrine system. Short-term exposure to high levels impairs the liver function and causes chloracne. The most sensitive population to dioxin exposure are the foetuses and infants.A large number of health effects have been documented in the scientific literature, and they all place dioxins among the most toxic chemicals known to man.
Human C-reactive protein (CRP) is a reactant involved in the acute phase response and one of the many molecular factors involved in pathogenesis of coronary artery disease (CAD). CRP gene variants ...potentially mediate CRP plasma concentrations and the development of CAD. 220 Croatian subjects with angiographically confirmed CAD and 132 control subjects were included in the study. CRP gene polymorphisms 1059G/C and -717G/A were determined by RFLPs, using MaeIII and KspI endonuclease, respectively. Plasma concentrations of CRP and homocysteine were determined by immunoturbidimetry and FPIA, respectively. CRP 1059G/C gene variants were significantly associated with CAD (OR = 0.50; 95% CI = 0.27, 0.94; P = 0.032). Wild GG genotype and rare allele C carrier genotypes were 184 and 22 in CAD(+) group, and 101 and 24 in CAD(-) group, respectively. Multivariate analysis with age, gender, BMI, smoking status, hypertension and diabetes as covariates showed that 1059C carriers had lower CRP concentrations in CAD(-) (P = 0.010) and CAD(+) subjects (P = 0.028). This allele was also significantly associated with lower plasma homocysteine concentrations in both groups (P = 0.018 for CAD(-) and 0.002 for CAD(+). There was no significant difference between CAD(+) and CAD(-) subjects in absolute frequencies for CRP -717A/G gene variant, but multivariate analysis showed that carriers of the rarer G allele had significantly higher CRP plasma concentrations in CAD(-) subjects (P = 0.031) and higher homocysteine concentrations in CAD(+) group (P < 0.001). Atherosclerosis is an inflammatory disease resulting from different genetic and environmental factors. Results presented here support the contribution of CRP genetic variations in the development of CAD.
Arterial thrombosis is the major reason for severe complications of coronary artery disease (CAD). Recently it has been suggested that the FXIII-A Val34Leu polymorphism, affecting clot stability, ...provides protection against thrombosis. Results published up to date implicate that there is a significant correlation between geographical area and the Leu34 allele prevalence and that its contribution to arterial thrombosis is different in different populations. The purpose of this study was to determine frequency of Leu34 allele in Croatian subjects as well as to estimate its association with a CAD. FXIII-A Val34Leu genotyping was carried out by real-time PCR method on the LightCycler using melting curve analysis with forward 5'-AACTTCCAGGACCGGCTTT-3' and reverse 5'-ACCCAGAGTGGTGGGGAA-3' primers. The Leu34 allele frequency in studied Croatian subjects was 24.3%. No significant differences were found in the prevalence of FXIII-A Val34Leu genotype or Leu34 allele distribution between studied subjects (P > 0.05). Carriage of the Leu34 allele was not significantly associated with CAD or MI risk reduction (P > 0.05). This is the first report that studies the prevalence of the Leu34 allele frequency in Croatian subjects and our results suggest that possession of the Leu 34 alele does not provide protection against MI.
Background: Familial LPL deficiency is a rare inborn error of metabolism caused by mutational change within the LPL gene, which leads to massive hypertriglyceridemia.
Methods: The underlying ...molecular defect in a boy of Croatian descent was studied by SSCP analysis, DNA sequencing and finally confirmed by RFLP.
Results: DNA analysis showed the child to be a homozygote and his parents heterozygotes for TGG→CGG change in codon 86 of the LPL gene, which leads to W86R amino acid substitution. DNA sequence analysis also showed a silent mutation in the third exon of father's DNA, V108V. Determination of some LPL gene polymorphisms showed the child and his parents to have
HindIII/H+H+ and both S447 wild-type alleles, whereas for
PvuII the parents had P
+P
− and the child P
+P
+ genotype.
Conclusions: In this case, W86R mutation was the reason for the production of nonfunctional enzyme and consequently triacylglycerol (TG) exceeding 15 mmol/l. This implies the risk of frequent episodes of acute pancreatitis. Decreased LPL activity leads to elevated triacylglycerol levels and reduced HDL-cholesterol, both risk factors for the development of coronary artery disease. LPL genotyping especially of young patients with hypertriglyceridemia is therefore necessary and justifiable.
Increased serum bilirubin levels in patients with Gilbert syndrome (GS) are caused by reduction of hepatic activity of bilirubin glucuronosyltranferase to about 30% of normal. UGT1A1 genetic ...polymorphism with absent or very low bilirubin UDP-glucuronosyltransferase (B-UGT) activity is associated with Gilbert's syndrome (GS) and other hyperbilirubinemias. The genetic basis of GS is the insertion of two additional TA nucleotides (resulting in seven repeats of TA) in the TATAA box, present in proximal promoter of UGT1A1 gene. This study included 323 Croatian pre-scholars, including 164 boys and 159 girls. Statistical analysis showed significant difference for total bilirubin concentration between different genotypes (p < 0.001). Also, statistically significant difference for total bilirubin concentration was emphasized between genotypes 6/6 and 7/7 (p < 0.001) as well as 6/7 and 7/7 (p < 0.001). Higher total plasma bilirubin concentrations are significantly correlated with 7/7 genotype which is present in 9.8% of population studied.
Modifications in lipoprotein lipase levels lead to elevated triglycerides and reduced high density lipoprotein (HDL), both of which are risk factors for coronary artery disease (CAD). Hence, we ...examined the influence of the −93T/G, D9N, N291S, and S447X polymorphisms in the lipoprotein lipase (LPL) gene on CAD risk and lipid levels in Croatian patients with and without angiographically confirmed CAD. The N291S polymorphism was significantly associated with CAD (OR = 0.36; 95% CI = 0.13, 0.99; p = 0.048). This association was only moderately affected by adjusting for various lipids (OR = 0.36; 95% CI = 0.12, 1.08; p = 0.068). HDL2-cholesterol and apolipoprotein A-I levels were significantly higher in non-carriers of the −93T/G and D9N polymorphisms in the CAD group (p = 0.017 and 0.028, respectively). The N291S genetic variant did not show any significant difference between carriers and non-carriers in either group studied for any of the lipids. Lower triglyceride and higher HDL2-cholesterol levels in the control group were associated with carriers of the S447X mutation (p = 0.043 and 0.056, respectively). LPL gene polymorphisms might be involved in predisposition to CAD and determination of lipid profiles.
This study was performed to assess the effect of the S447X and Hind III lipoprotein lipase gene polymorphisms on development of coronary artery disease and hypertriglyceridemia. The study included ...132 patients and 98 healthy control subjects of Croatian descent. The lipoprotein lipase S447X polymorphism was associated with coronary artery disease and hypertriglyceridemia, as indicated by the lower frequency of S447 allele in the patient group (p = 0.005) and odds ratio (O.R = 0.40, p = 0.006). The patient and control groups also showed a significant difference in the distribution of Hind III/S447X genotype combinations (p = 0.013). There were no significant associations with lipid parameters for any genotype or genotype combination in the patient group. Frequencies of the S447X polymorphism and S447X/Hind III combinations differed between the CAD/TG and control group, thus these polymorphisms may be associated with CAD and hypertriglyceridemia.