Diabetic nephropathy (DN), the most serious complication of Type 1 diabetes (DM1), has a strong genetic component. Cyclooxygenase-2 (COX-2), an in ducible enzyme by a number of stimuli, has been implicated in pathophysiology of cardiovascular and renal disease, including DN. The allele -765C, of the -765G>C polymorphism (rs20417) in the COX-2 promoter has lower promoter activity compared with the -765G allele and protective effects in cardiovascular disease. This polymorphism was not investigated in patients with DM1 and nephropathy. The study was conducted in 779 Caucasian patients with DM1 and compared to a representative sample of healthy Czech population. The patients demonstr ated lower frequencies of the CC genotype (P=0.005). From th e DM1 cohort, 153 patients met the criteria for low risk of the development of DN (LRDN, duration of DM1>10 years, normoalbuminuria, normotension) and 139 patients had manifest DN. There were no differences in -765G>C polymorphisms between LRDN and DN patients. Moreover, the C/G allele frequenc ies did not also differ between the groups. In conclusion, patients with DM1 display lower freqencies of the protective CC genotype as compared to healthy subjects. However, the study did not reveal associations of -765G>C polymorphism with the risk of DN., J. A. Hubáček ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Genes for adiponectin and resistin are candidate genes of insulin resistance and type 2 diabetes mellitus. The aim of our study was to determine the frequency of single nucleotide polymorphisms (SNP) 45T>G and 276G>T of the adiponectin gene and 62G>A and -180C>G of the resistin gene in patients with obesity (OB), anorexia nervosa (AN) and in control healthy normal-weight women (NW) and to study the influence of particular genotypes on serum concentrations of these hormones and on insulin sensitivity. Serum adiponectin, resistin, tumor necrosis factor alpha (TNF-alpha), insulin, cholesterol, glycated hemoglobin (HbA1c) and blood glucose levels were measured in 77 patients with OB, 28 with AN and 38 NW. DNA analysis was carried out by polymerase chain reaction with restriction analysis of PCR product. The presence of SNP ADP+276 G>T allele was accompanied by higher cholesterol levels in AN patients, higher adiponectin concentrations in OB patients and lower HbA1c levels in NW. SNP of the resistin gene 62G>A was associated with lower HbA1c in NW and higher cholesterol concentrations in OB group. The carriers of the minor G allele in the position -180 of the resistin gene within AN group had significantly higher BMI relative to non-carriers. We conclude that polymorphisms in adiponectin and resistin genes can contribute to metabolic phenotype of patients with obesity and anorexia nervosa., J. Křížová, M. Dolinková, Z. Lacinová, Š. Sulek, R. Doležalová, J. Housová, J. Krajíčková, D. Haluzíková, L. Bošanská, H. Papežová, M. Haluzík., and Obsahuje bibliografii a bibliografické odkazy
High plasma levels of triglycerides (TG) are an independent risk factor in the development of cardiovascular disease, with about 50 % of the final levels being determined genetically. Apolipoprotein A5 ( APOA5 ) is the last discovered member of the apolipoprotein APOA1/C3/A4 gene cluster, found by comparative sequencing analysis. The importance of APOA5 gene for determination of plasma triglyceride levels has been suggested after development of transgenic and knock-out mice (transgenic mice displayed significantly reduced TG, whereas knock-out mice had high TG). In Czech population, alleles C-1131 and Trp19 are associated with elevated levels of plasma TG and higher risk of myocardial infarction development. These alleles also play some role in nutrigenetics and actigenetics of lifestyle interventions leading to the plasma cholesterol changes as well as in the pharmacogenetics of statin treatment. On the contrary, APOA5 mutations detected in Czech population did not show strict effect on plasma TG levels. Val153 → Met variant exhibit the sex-specific effect of HDL-cholesterol levels. The suggested roles of APOA5 variants in determination of the plasma remnant particles, plasma concentrations of C-reactive protein or some anthropometrical parameters were excluded., J. A. Hubáček ... [et al.]., and Obsahuje seznam literatury
Apolipoprotein B (apo B) is the major protein component of LDL, VLDL and chylomicrons. Numerous polymorphisms of the apolipoprotein B gene have been described. Particularly, the insertion/deletion polymorphism located in the coding part of the signal peptide of apo B, associated with modification of lipid concentrations and the risk of cardiovascular disease, has been reported in the general population. No such study in the Tunisian population has been performed. The aim of our study was to assess the effect of insertion/deletion polymorphism of the apolipoprotein B gene on lipid levels in a sample of the Tunisian population. A total of 458 unrelated subjects (321 men and 137 women) were included. The insertion/deletion polymorphism was determined by electrophoresis on polyacrylamide gels after PCR amplification. The relative frequencies of the Ins and Del alleles were 0.74 and 0.26, respectively. These frequencies were similar to those found in other Caucasian populations. There was no significant difference in serum TC, TG, and HDL-C levels due to the influence of the genotypes. However, significant variation among the three genotypes was seen for LDL-cholesterol (p<0.001) and apo B (p<0.001) levels. Individuals homozygous for the Del allele had higher levels than individuals homozygous for the Ins allele, while individuals heterozygous for both alleles exhibited intermediate levels. When the data were analyzed in men and women separately, a similar effect was seen in both groups. Our results show that distribution of apo B insertion/deletion polymorphism in Tunisians is similar to other Caucasian population and confirm the reported association with serum LDL-cholesterol and apo B concentrations., A. Kallel, M. Fekl, M. Elasmi, M. Souissi, H. Shanhaji, S. Omar, S. Haj Taieb, R. Jemaa, N. Kaabachi., and Obsahuje bibliografii a bibliografické odkazy
The aim of this study was to evaluate the association of A1166C polymorphism in angiotensin II type 1 receptor (AT1R) gene with baroreflex sensitivity (BRS in ms/mm Hg; BRSf in mHz/mm Hg) in man. BRS and BRSf were determined by a spectral method in 135 subjects (19-26 years) at a frequency of 0.1 Hz. Genotypes were detected by means of polymerase chain reaction and restriction analysis using enzyme DdeI. We compared BRS and BRSf among genotypes of this polymorphism. The frequency of genotypes of AT1R A1166C polymorphism was: 45.9 % (AA, n=62), 45.9 % (AC, n=62), 8.2 % (CC, n=11). Differences in BRS (p<0.05) and BRSf (p<0.01) among genotypes of this single nucleotide polymorphism were found (Kruskal-Wallis: BRS - AA: 7.9±3.3, AC: 8.6±3.6, CC: 5.9±2.3 ms/mm Hg; BRSf - AA: 12.0±4.0, AC: 12.0±5.0, CC: 8.0±3.0 mHz/mm Hg). Compared to carriers of other genotypes (AA+AC) the homozygotes with the less frequent allele (CC) showed significantly lower BRSf (Mann-Whitney: BRSf - AA+AC: 12.0±4.0, CC: 8.0±3.0 mHz/mm Hg; p<0.01) and borderline lower BRS (BRS - AA+AC: 8.2±3.5, CC: 5.9±2.5 ms/mm Hg; p=0.07). We found a significant association of A1166C polymorphism in AT1 receptor gene with baroreflex sensitivity. Homozygosity for the less frequent allele was associated with decreased baroreflex sensitivity., M. Jíra ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
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
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
Variants within the FTO gene are important determinants of body mass index (BMI), but their role in determination of BMI changes after combined dietary/physical ac tivity intervention is unclear. We have analyzed 107 unrelated overweight non-diabetic Czech females (BMI over 27.5 kg/m2 , age 49.2±12.3 years). FTO variants rs17817449 (first intron) and rs17818902 (third intron) were genotyped. The life style mo dification program (10 weeks) consisted of an age- matched reduction of energy intake and exercise program (aerobic exercise 4 times a week, 60 min each). The mean BMI before intervention was 32.8±4.2 kg/m2 and the mean achieved weight loss was 4.8±3.5 kg (5.3±3.5 %, max. -15.5 kg, min. +2.0 kg, p<0. 01). No significant association between BMI decrease and FTO variants was found. Also waist-to-hip ratio, body composition (body fat, water, active tissue), lipid parameters (total, LDL and HDL cholesterol, triglycerides) glucose and hsCRP change s were independent on FTO variants. FTO variants rs17817449 and rs17818902 are not associated with BMI changes after combined short time dietary/physical activity intervention in overweight females., D. Dlouhá ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Numerous association studies have been involved in studying the angiotensinogen (AGT) variants, AG T plasma levels and relations to cardiovascular diseases, such as hypertension, myocardial infarction, coronary heart disease. To investigate a role of AGT G(-6)A and M235T genetic variants for chronic heart failure (CHF) and advanced atherosclerosis (AA), a total of 240 patients with CHF and 200 patients with AA of the Czech origin were evaluated for the study. The study shows the role of polymorphism AGT G(-6)A in genetic background among advanced atherosclerosis patients and chronic heart failure patients (Pg=0.001). This difference was also observed in comparison of AA patients with subgroup of CHF with dilated cardiomyopathy (Pg=0.02; Pa=0.009), and ischemic heart disease (Pg=0.007). The greatest difference between triple-vessel disease and chronic heart failure groups was observed in freque ncy of GT haplotype (P<0.001) and GGMT associated genotype (P <0.001). Retrospectively, we found the same trend when the subgroups of CHF were compared to AA group (AA vs. IHD with CHF P<0.001; AA vs. DCM P<0.001). These results suggest AGT genetic variants as a risk factor for chronic heart failure compared to advanced atherosclerosis disease without heart failure, with a strong difference between IHD patients and chronic heart failure patients with ischemic heart disease, especially in haplotypes and associated genotypes., M. Pávková Goldbergová ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy