The LRP5 gene is believed to be primarily associated with bone metabolism via Wnt signaling. The latter pathway, however, appears to control various other systems outside the skeleton. To find the relationships of the LRP5 gene to serum follicle stimulating hormone (FSH ) and luteinizing hormone (LH) in the cohort of normal postmenopausal women, we identified the C/T (c.4037:A1330V) polymorphism in the LRP5 gene using a restriction analysis of the PCR product in a cohort of 165 untreated pre- and post-menopausal women. In a subset of 111 post-menopausal women we analyzed the association between the LRP5 genotype and serum levels of sex-hormones including FSH and LH. The distribution of CC, TC and TT genotypes of the C/T polymorphism in the whole group was 73.9 %, 23.6 % and 2.4 %, respectively, which is comparable with other Caucasian populations. As no TT homozygote was found in the group of post-menopausal women, serum sex-hormones were compared between CC and TC genotypes. Women with the CT allele combination had markedly higher serum FSH levels as compared to carriers of the CC genotype (p<0.004). No differences between these genotypes were found in serum LH levels as well as the circulating sex-steroids such as estradiol, testosterone, dehydroepiandrosterone and/or its sulphate, androstenedione and SHBG. To conclude, the LRP5 gene is associated with circulating FSH in normal post-menopausal women in the present study. The mediating role of subtle undetectable variations in estrogen levels is discussed. We did not find any relationship between the LRP-5 genotype and serum LH levels., I. Žofková, M. Hill, K. Zajíčková., and Obsahuje bibliografii a bibliografické odkazy
The aim of this study was to evaluate the association of single nucleotide polymorphisms (SNPs) T-786C and G894T in the gene encoding eNOS with blood pressu re variability (BPV) in man. Blood pressure was recorded beat-t o-beat at rest three times in periods of one week (5 min, Finapres, breathing at 0.33 Hz) in 152 subjects (19-24 years). Systolic (SBPV0.1r/SBPV 0.1a) and diastolic (DBPV0.1r/DBPV 0.1a) blood pressure variabilities in relative (r.u.) and absolute (mmHg2/Hz) units were determined by the spectral method as spectral po wer at the frequency of 0.1 Hz. Genotypes of both polymorphisms were detected using polymerase chain reaction and re striction analysis using enzymes Msp I and Ban II. Significant diffe rences were observed in BPV among genotypes of T-786C SNP (p<0.05; Kruskal-Wallis), and among haplotypes of both SNPs (p<0.05; Kruskal-Wallis) as well. In T-786C SNP, carriers of less frequent allele (CC homozygotes and TC heterozygotes) showed significantly greater SBPV0.1r and SBPV0.1a compared to TT homozygote s (Mann-Whitney; p<0.05). The G894T variant showed no sign ificant differences, but, both SNPs were in linkage disequilib rium (D’=0.37; p<0.01). Carriers of haplotype CT/CT (CC homozygotes of -786C/T and TT homozygotes of G894T) displaye d significantly greater SBPV0.1r, SBPV0.1a and DBPV0.1a compared to carriers of other haplotype combinations (Kruskal-Wallis; p=0.015, p=0.048, and p=0.026, respectively). In conclusion, the haplotype formed by less frequent alleles of both eNOS variants was associated with increased systolic and diastolic BPV in this study., M. Jíra ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
A predominance of small, dense low-density lipoproteins (LDL) is characteristic of the dyslipidemic state seen in type 2 diabetes. However, no study has investigated the association in gestational diabetes mellitus (GDM), which is pathophysiologically similar to type 2 diabetes. We hypothesized that LDL particle size is reduced in GDM cases compared with controls. Gradient gel electrophoresis was used to characterize LDL subclass phenotypes in non-fasting intrapartum plasma from 105 GDM cases and 96 controls. All participants were free of pre-existing diabetes or hypertension. The authors used logistic regression to estimate odds ratios (OR) and 95 % confidence intervals (CI) adjusted for confounders. Women with this phenotype had a significant 4.9-fold (95 % CI: 1.1-23.2) increased risk of GDM compared with those with the large, buoyant phenotype. The magnitude of this association was attenuated when plasma triglyceride and other confounders were included in the model (OR=4.2, 95 % CI: 0.5-39.5). Mean LDL particle size in GDM cases was smaller compared with controls (270.1 vs. 272.7Å, p=0.003). The OR of GDM risk was 1.8 (95 % CI: 0.9-3.3) for every 10-Å reduction in LDL particle size. Large prospective studies are needed to evaluate the association between smaller LDL particle size in early pregnancy with subsequent GDM risk., C. Qiu, C. Rudra, M. A. Austin, M. A. Williams., and Obsahuje bibliografii a bibliografické odkazy
We assessed association between novel biomarkers of cardiovascular disease and conven tional factors in 40 years old subjects (208 men and 266 women) from the general population of Slovakia. FER HDL (cholesterol esterifi cation rate in HDL plasma), AIP - Atherogenic Index of Plasma [Log(TG/HDL-C)] as markers of lipoprotein particle size, and CILP2, FTO and MLXIPL polymorphisms, were examined in relation to biomarkers and conventional risk factors. Un ivariate analyses confirmed correlation between AIP, FERHDL and the most of measured parameters. Relations between AIP and CILP2, FTO and MLXIPL were not significant. However, CILP2 was significantly related to FERHDL in both genders. In multivariate analysis BMI was the strongest correlate of AIP levels. In multivariate model variability of FER HDL was best explained by AIP (R2 =0.55) in both genders with still significant effect of CILP2 SNP in men. In a model where AIP was omitted, TG leve ls explained 43 % of the FER HDL variability in men, while in women HDL-C was the major determinant (42 %). In conclusions, FERHDL and AIP related to the known markers of cardiovascular risk provide means to express their subtle interactions by one number. Our novel finding of association between CILP2 polymorphism and FERHDL supports its role in lipid metabolism., K. Rašlová ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Insulin resistance is present in patients with Type 2 diabetes mellitus as well as in obese patients without diabetes. The aim of our study was to compare insulin action in diabetic and control persons with or without obesity and to evaluate the influence of serum cholesterol, serum triglyceride and blood pressure on metabolic variables of insulin action. We examined 42 Type 2 diabetic patients and 41 control persons with body mass index (BMI) from 21.1 to 64.5 kg.m-2, and 33 to 71 years old. The isoglycemic hyperinsulinemic clamp technique was performed at an insulin infusion rate of 1 mU.kg-1.min-1 during 120 min. We evaluated the metabolic clearance rate of glucose (MCRG, ml.kg-1.min-1) as the most important indicator of insulin action by isoglycemic clamp. The Pearson's correlation and multiple regression models were used to compare studied factors with the insulin action. We found following predictors of insulin resistance expressed in the relationship with MCRG: BMI (r = -0.68, p<0.001), plasma glucose concentration (r = -0.66, p<0.001), cholesterol (r=-0.55, p<0.001), triglycerides (r = -0.54, p<0.001) and mean blood pressure (r = -0.38, p<0.01). From the multiple regression analysis we conclude that obesity may have even greater influence on the insulin action than diabetes mellitus itself., G. Šindelka, J. Škrha, M. Prázný, T. Haas., and Obsahuje bibliografii
The aldosterone synthase gene (CYP11B2) is an important candidate gene region in essential hypertension. We therefore studied the association of -344T/C polymorphism of the CYP11B2 gene with the presence and severity of hypertension in a case-control study. We studied 369 individuals, of whom 213 were hypertensive patients (139 controlled hypertensive, 74 resistant hypertensive) and 156 were healthy normotensive subjects. The -344T/C polymorphism of the CYP11B2 gene was determined using polymerase chain reaction - restriction fragment length polymorphism analysis. The distribution of genotypes in normotensive controls and hypertensive subjects were: TT 25.6 vs. 31.9 %, TC 51.9 vs. 57.3 % and CC 22.4 vs. 10.8 %. The -344T/C variant was associated with hypertension. Subjects carrying the -344T allele had a greater risk of hypertension compared to those having C allele (χ2=5.89, p<0.05). The frequency of CC genotype was significantly lower in hypertensive patients than in normotensive controls ( χ2=9.44, p<0.01). A stepwise logistic regression analysis confirmed these findings. We did not find an association of -344T/C variant with the resistance of hypertensive patients to combination therapy, but we observed an association of -344T/C polymorphism of aldosterone synthase gene with increased risk of hypertension. These results support a potential role of -344T/C CYP11B2 gene polymorphism in genetic predisposition to develop hypertension., Z. Hlubocká ... [et al.]., and Obsahuje seznam literatury
Atrial fibrosis is considered as the basis in the development of long-standing atrial fibrillation (AF). However, in advanced heart failure (HF), the independent role of fibrosis for AF development is less clear since HF itself leads to atrial scarring. Our study aimed to differentiate patients with AF from patients without AF in a population consisting of patients with advanced HF. Myocardial samples from the right atrial and the left ventricular wall were obtained during he art transplantation from the explanted hearts of 21 male patients with advanced HF. Long- standing AF was present in 10 of them and the remaining 11 patients served as sinus rhythm controls. Echocardiographic and hemodynamic measurements were recorded prior to heart transplantation. Collagen volume fraction (CVF), transforming growth factor-beta (TGF- β ), and connective tissue growth factor (CTGF) expression in myocardial specimens were assessed histologically and immunohistochemically. The groups were well matched according to age (51. 9±8.8 vs. 51.3±9.3 y) and co- morbidities. The AF group had high er blood pressure in the right atrium (13.6±7.7 vs. 6.0±5.0 mmHg; p=0.02), larger left atrium diameter (56.1±7.7 vs. 50±5.1 mm; p=0.043), higher left atrium wall stress (18.1±2.1 vs. 16.1±1.7 kdynes/m 2 ; p=0.04), and longer duration of HF (5.0±2.9 vs. 2.0±1.6 y, p=0.008). There were no significant differences in CVF (p=0.12), in CTGF (p=0.60), and in TGF- β expression (p=0.66) in the atrial myocardium between the two study groups. In conclusions, in advanced HF, atrial fibrosis expressed by CVF is invariably present regardless of occurrence of AF. In addition to atrial wall fibrosis, increased wall stress might contribute to AF development in long-standing AF., B. Aldhoon, ... [et al.]., and Obsahuje seznam literatury
Concentrations of numerous hormones decrease with age. Some authors imply that a syndrome of partial endocrine deficiency may occur in the aging men. Among many lifestyle factors that influence hormonal status is physical activity. Especially interesting are relations between physical activity and the androgenic/estrogenic status of men. The aim of this study was to evaluate age-related changes of serum androgens, estradiol and SHBG in men presenting different levels of physical activity. Hormonal parameters were measured in a cohort of 387 healthy Caucasian men (aged from 24 to 72 years) from one administrative region of Poland. Their level of physical activity was determined by means of the International Physical Activity Questionnaire (IPAQ). We have found that contrary to SHBG concentration, total testosterone, free testosterone, bioavailable testosterone, calculated free testosterone and estradiol were negatively associated with age in the investigated subjects. Apart from estradiol, physical activity did not influence concentrations of the studied parameters. In younger (24-48 years), physically active males estradiol was significantly higher than in subjects characterized by a low level of physical activity. The situation was opposite in older males (48-72 years). In this age group low level of physical activity was associated with lower concentration of estradiol. Undertaking physical effort increased the decline of estradiol level with age., M. Slowinska-Lisowska, P. Jozkow, M. Medras., and Obsahuje bibliografii a bibliografické odkazy
Level of asymmetric dimethylarginine (ADMA) is elevated and endothelial progenitor cells (EPC) and stem cells (SC) are decreased in patients undergoing renal transplantation (Tx) and may contribute to cardiovascular complications. We tested the hypothesis that ADMA, EPC and SC can be influenced with regular physical exercise early after Tx. Blood samples of ADMA, EPC, SC, adipocytokines and metabolic parameters were randomly obtained from 50 transplant patients before and 6 months after exercise program (Group I). Fifty age, sex HLA typing, duration of dialysis and immunosupression regimen-matched non exercising transplant were examined as controls (Group II). After 6 months, in Group I ADMA decreased (3.50±0.45 vs 2.11±0.35 μmol/l, P<0.01) and was lower comparing to Grou II (P<0.01), SC and EPC also decreased (2816±600 vs 2071±480 cells/ml resp. 194±87 to 125±67 cells/ml, P<0.02). Next changes in Group I: adiponectin (P<0.01), leptin (P<0.01), resistin (P<0.02). Visfatin, blood lipids, HbA1c, insulin and blood pressure were also influenced by training program (P<0.05)., V. Teplan, I. Králová Lesná, J. Piťha, A. Mahrová, J. Racek, I. Valkovský, A. Sekerková, M. Štollová., and Obsahuje bibliografii
a1_In this study we compared several parameters characterizing differences in the lipoprotein profile between members of families with a positive or negative family history of coronary artery disease (CAD). In addition to regular parameters such as the body mass index (BMI), total plasma cholesterol (TC), low density (LDL-C) and high density (HDL-C) cholesterol and triglycerides (TG) we estimated the fractional esterification rate of cholesterol in apoB lipoprotein-depleted plasma (FERHDL) which reflects HDL and LDL particle size distribution. A prevalence of smaller particles for the atherogenic profile of plasma lipoproteins is typical. Log (TG/HDL-C) as a newly established atherogenic index of plasma (AIP) was calculated and correlated with other parameters. The cohort in the study consisted of 29 young (< 54 years old) male survivors of myocardial infarction (MI), their spouses and at least one offspring (MI group; n=116). The control group consisted of 29 apparently healthy men with no family history of premature CAD in three generations, their spouses and at least one offspring (control group; n=124). MI families had significantly higher BMI than the controls, with the exception of spouses. Plasma TC did not significantly differ between MI and the controls. MI spouses had significantly higher TG. Higher LDL-C had MI survivors only, while lower HDL-C had both MI survivors and their spouses compared to the controls. FERHDL was significantly higher in all the MI subgroups (probands 25.85±1.22, spouses 21.55±2.05, their daughters 16.93±1.18 and sons 19.05±1.33 %/h) compared to their respective controls (men 20.80±1.52, spouses 14.70±0.98, daughters 13.23±0.74, sons 15.7±0.76 %/h, p<0.01 to p<0.05). Log (TG/HDL-C) ranged from negative values in control subjects to positive values in MI probands., a2_High correlation between FERHDL and Log (TG/HDL-C) (r = 0.80, p<0.0001) confirmed close interactions among TG, HDL-C and cholesterol esterification rate. The finding of significantly higher values of FERHDL and Log (TG/HDL-C) indicate higher incidence of atherogenic lipoprotein phenotype in members of MI families. The possibility that, in addition to genetic factors, a shared environment likely contributes to the familial aggregation of CAD risk factors is supported by a significant correlation of the FERHDL values within spousal pairs (control pairs: r = 0.51 p<0.01, MI pairs: r = 0.41 p<0.05)., M. Dobiášová, K. Rašlová,H. Rauchová, B. Vohnout, K. Ptáčková, J. Frohlich., and Obsahuje bibliografii