Cíl: Vztah mezi hypercholesterolemií, zvláště zvýšenými hodnotami cholesterolu v lipoproteinech o nízké hustotě (lDl-c) a ischemickou chorobou srdeční (ichS), je potvrzen důkazy z předchozích epidemiologic kých studií. Důležité bylo popsání souvislosti mezi genetickým polymorfismem a hodnotami lipidů v plazmě. cílem této studie bylo zkoumat vztah mezi variantami rs5918 t>c genu pro itGB3 a variantou rs1799837 c>t ge nu pro APo-A1 na jedné straně a metabolismem lipidů v séru na straně druhé. Pacienti a metody: Do této studie bylo zařazeno celkem 100 jedinců s ichS a 250 zdravých jedinců. u každé ho účastníka bylo provedeno základní biochemické vyšetření včetně stanovení koncentrace glukózy v séru, celkového cholesterolu (total cholesterol, tc) v séru, hodnot hDl-c, lDl-c a triglyceridů. Pro genotypizaci polymorfismů genů pro itGB3 a APo-A1 byla použita polymerázová řetězová reakce s následnou analýzou polymorfismu délky restrikčních fragmentů (restriction fragment length polymorphism, rflP). Výsledky: Pokud se týče genotypu a distribuce alel polymorfismu rs5918 t>c genu pro itGB3, vyskytovala se alela c častěji ve skupině s ichS než v kontrolní skupině (p = 0,001). Ve skupině s ichS byla navíc pozorována statisticky významná souvislost mezi genotypem rs5918 itGB3 a hodnotami celkového cholesterolu v geno typu cc na jedné straně a tc v séru a cholesterolu v lipoproteinech o vysoké hustotě (hDl-c) (p = 0,0006, resp. p = 0,016). nicméně ani v kontrolní skupině, ani ve skupině s ichS nebyla nalezena statisticky významná spojitost mezi polymorfismem rs1799837 c>t genu pro APo-A1 a biochemickými parametry. Závěr: Výsledky prokázaly, že varianta rs5918 t>c genu pro itGB3 by mohla být z klinického hlediska vý znamná jako genetický marker zvýšené vnímavosti k rozvoji ichS. Alelu c varianty rs5918 genu pro itGB3 by tak bylo možno navrhnout pro screening potenciálního rozvoje ichS u populace kyperských turků, kteří se dostaví na kontrolu k lékaři.

Aim: The relationship between hypercholesterolemia, particularly elevated low density lipoprotein-cholesterol (LDL-C) levels and coronary artery disease is recognized by the evidence from previous epidemiologic studies. Importantly, genetic polymorphisms on different genes have been reported to be associated with plasma lipid levels. In this particular study, we aimed to investigate the relationship between the ITGB3 gene rs5918 T>C and APO-A1 gene rs1799837 C>T markers and serum lipid metabolism. Patients and methods: A total of 100 subjects with CAD and 250 healthy subjects were involved in the current study. A basic biochemical analysis, including serum glucose, total serum cholesterol, HDL-C, LDL-C and triglycerides, was performed for each participant. Genotyping for the ITGB3 gene and APO-A1 gene polymorphisms was performed by polymerase chain reaction followed by restriction fragment length polymorphism (RFLP) analysis. Results: With respect to the genotype and allele distributions of ITGB3 rs5918 T>C polymorphism, the frequency of the C allele was higher in the coronary artery disease (CAD) group compared to the control group (p = 0.001). Moreover, there was a statistically significant association detected between ITGB3 rs5918 CC genotype and serum total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C) (p = 0.0006, p = 0.016, respectively) in CAD group. However there was no statistically significant association was identified between the APOA1 rs1799837 C>T polymorphism and biochemical parameters in control and CAD group. Conclusion: The results demonstrated that rs5918 T>C variant within the ITGB3 gene might have a clinical importance as a genetic marker which increases the susceptibility to CAD. Therefore, the ITGB3 gene rs5918 C allele may be offered as a screening option for CAD in Turkish Cypriot population who come in for medical check-up.

Background: Statin intolerance is a serious therapeutic dilemma in secondary cardiovascular prevention (e.g., ESC/EAS Guidelines 2023). This is especially true when confirmed by genetic predisposition and complicated by rhabdomyolysis. Although several non-statin agents have become available in recent years, evidence regarding their combined use in high-risk statin-intolerant patients remains limited. Furthermore, the pharmacokinetics of statins in toxic concentrations are poorly characterized in clinical settings. Case Presentation: We present two cases of genetically confirmed statin-induced rhabdomyolysis, both accompanied by severe acute kidney injury requiring renal replacement therapy. In both patients, serial measurements of rosuvastatin plasma concentrations revealed markedly delayed elimination, with detectable levels persisting for several weeks despite ongoing dialysis. Estimated half-lives exceeded 7 days in both cases, far beyond the known therapeutic range. Genetic testing identified SLCO1B1, ABCB1, and CYP2C9 polymorphisms linked to reduced hepatic uptake and impaired drug clearance. Following biochemical recovery, both patients were initiated on a triple non-statin lipid-lowering regimen consisting of ezetimibe, bempedoic acid, and inclisiran. The combination was well tolerated, with no recurrence of muscle-related symptoms or biochemical toxicity. LDL-C levels were reduced from 3.05 to 1.59 mmol/L and from 4.99 to 1.52 mmol/L, respectively, with sustained response over 12 and 40 weeks. Full lipid profiles demonstrated favorable changes across all parameters. Conclusions: These two cases suggest that the combination of ezetimibe, inclisiran, and bempedoic acid may serve as a safe and effective therapeutic option in patients with severe statin intolerance. Pharmacogenetic testing and serial pharmacokinetic assessment may guide personalized lipid-lowering strategies and improve outcomes in this challenging patient population.

• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH

Díky svému umístění chrání hydrofobní lipidová doména paraoxonázy-1 (PON-1) lipoproteiny o vysoké hustotě (high-density lipoprotein, HDL), lipoproteiny o nízké hustotě (low-density lipoprotein, LDL) a buněčné membrány na vnější straně před oxidací. Nezastavuje se tím tvorba konjugovaných dienů, ale mění se tak produkty lipoperoxidace na neškodné karboxylové kyseliny místo aldehydů, které by se mohly navazovat na apolipoprotein B. Paraoxonáza-1 v séru negativně ovlivňuje nové příhody u diabetu a aterosklerotického kardiovaskulárního onemocnění (ASKVO). Diabetes, dyslipidemie a zánět snižují aktivitu PON-1. Ablace lidského genu pro PON-1 nebo nadměrná exprese tohoto genu u zvířat posiluje nebo tlumí vnímavost k rozvoji aterosklerózy. Na rozdíl od apolipoproteinu AII zvyšují sérová koncentrace amyloidu A a myeloperoxidáza, apolipoprotein AI a poměr lecitin : cholesterol acyl transferáza antioxidační účinek PON-1. Strava a již užívané léky měnící hodnoty lipidů mohou účinnost PON snížit, je však třeba provádět specifickou léčbu zvyšující hodnoty PON-1.

Due to where paraoxonase-1 (PON-1)'s hydrophobic lipid domain is located, high-density lipoprotein (HDL) protects low-density lipoprotein (LDL) and the cell membranes on the outside from oxidation. It doesn't stop the formation of conjugated dienes, but it changes the products of lipid peroxidation into harmless carboxylic acids instead of aldehydes that could link to apolipoprotein B. Serum PON-1 inversely affects new events in diabetes and atherosclerotic cardiovascular disease (ASCVD). Diabetes, dyslipidemia, and inflammation decrease PON-1 activity. Human PON-1 gene ablation or overexpression in animals enhances or reduces atherosclerosis susceptibility. Unlike AII, serum amyloid A, and myeloperoxidase, apolipoprotein AI and lecithin : cholesterol acyl transferase boost PON-1 antioxidant activity. Diet and pre-existing lipid-modifying drugs may impact PON-1 activity, but specific PON-1-raising therapy is required.

• MeSH
• aryldialkylfosfatasa * fyziologie   genetika   krev   škodlivé účinky   MeSH
• ateroskleróza * genetika   krev   MeSH
• kardiovaskulární nemoci diagnóza   terapie   MeSH
• klinická studie jako téma MeSH
• lidé MeSH
• lipoproteiny HDL fyziologie   MeSH
• lipoproteiny MeSH
• peroxidace lipidů fyziologie   MeSH
• polymorfismus genetický fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

BACKGROUND: The highest mortality and morbidity worldwide is associated with atherosclerotic cardiovascular disease (ASCVD), which has in background both environmental and genetic risk factors. Apolipoprotein L1 (APOL1) variability influences the risk of ASCVD in Africans, but little is known about the APOL1 and ASCVD in other ethnic groups. METHODS: To investigate the role of APOL1 and ASCVD, we have genotyped four (rs13056427, rs136147, rs10854688 and rs9610473) APOL1 polymorphisms in a group of 1541 male patients with acute coronary syndrome (ACS) and 1338 male controls. RESULTS: Individual APOL1 polymorphisms were not associated with traditional CVD risk factors such as smoking, hypertension or diabetes prevalence, with BMI values or plasma lipid levels. Neither individual polymorphisms nor haplotypes were associated with an increased risk of ACS nor did they predict total or cardiovascular mortality over the 10.2 ± 3.9 years of follow-up. CONCLUSIONS: We conclude that APOL1 genetic variability has no major effect on risk of ACS in Caucasians.

• MeSH
• akutní koronární syndrom * genetika   MeSH
• apolipoprotein L1 * genetika   MeSH
• apolipoproteiny genetika   MeSH
• běloši genetika   MeSH
• genetická predispozice k nemoci MeSH
• haplotypy MeSH
• jednonukleotidový polymorfismus MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipoproteiny HDL genetika   MeSH
• rizikové faktory MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH

BACKGROUND: The associations of risk factors with vascular impairment in type 1 diabetes patients seem more complex than that in type 2 diabetes patients. Therefore, we analyzed the associations between traditional and novel cardiovascular risk factors and vascular parameters in individuals with T1D and modifications of these associations according to sex and genetic factors. METHODS: In a cross-sectional study, we analyzed the association of risk factors in T1D individuals younger than 65 years using vascular parameters, such as ankle brachial index (ABI) and toe brachial index (TBI), duplex ultrasound, measuring the presence of plaques in carotid and femoral arteries (Belcaro score) and intima media thickness of carotid arteries (CIMT). We also used photoplethysmography, which measured the interbranch index expressed as the Oliva-Roztocil index (ORI), and analyzed renal parameters, such as urine albumin/creatinine ratio (uACR) and glomerular filtration rate (GFR). We evaluated these associations using multivariate regression analysis, including interactions with sex and the gene for connexin 37 (Cx37) polymorphism (rs1764391). RESULTS: In 235 men and 227 women (mean age 43.6 ± 13.6 years; mean duration of diabetes 22.1 ± 11.3 years), pulse pressure was strongly associated with unfavorable values of most of the vascular parameters under study (ABI, TBI, Belcaro scores, uACR and ORI), whereas plasma lipids, represented by remnant cholesterol (cholesterol - LDL-HDL cholesterol), the atherogenic index of plasma (log (triglycerides/HDL cholesterol) and Lp(a), were associated primarily with renal impairment (uACR, GFR and lipoprotein (a)). Plasma non-HDL cholesterol was not associated with any vascular parameter under study. In contrast to pulse pressure, the associations of lipid factors with kidney and vascular parameters were modified by sex and the Cx37 gene. CONCLUSION: In addition to known information, easily obtainable risk factor, such as pulse pressure, should be considered in individuals with T1D irrespective of sex and genetic background. The associations of plasma lipids with kidney function are complex and associated with sex and genetic factors. The decision of whether pulse pressure, remnant lipoproteins, Lp(a) and other determinants of vascular damage should become treatment targets in T1D should be based on the results of future clinical trials.

• MeSH
• diabetes mellitus 1. typu * genetika   patofyziologie   MeSH
• diabetické angiopatie genetika   patofyziologie   MeSH
• dospělí MeSH
• fenotyp MeSH
• fotopletysmografie MeSH
• genetická predispozice k nemoci MeSH
• hodnoty glomerulární filtrace MeSH
• intimomediální šíře tepenné stěny MeSH
• lidé středního věku MeSH
• lidé MeSH
• polymorfismus genetický MeSH
• protein alfa 4 mezerového spoje * genetika   MeSH
• průřezové studie MeSH
• rizikové faktory kardiovaskulárních chorob MeSH
• sexuální faktory MeSH
• tlakový index kotník-paže MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The genetic basis of variability in drug response is at the core of pharmacogenomics (PGx) studies, aiming at reducing adverse drug reaction (ADR), which have interethnic variability. This study used the Kardiovize Brno 2030 random urban Czech sample population to analyze polymorphisms in a wide spectrum of genes coding for liver enzymes involved in drug metabolism. We aimed at correlating real life drug consumption with pharmacogenomic profile, and at comparing these data with the SUPER-Finland Finnish PGx database. A total of 250 individuals representative of the Kardiovize Brno 2030 cohort were included in an observational study. Blood DNA was extracted and 59 single nucleotide polymorphisms within 13 genes (BCHE, CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A5, F2, F5, IFNL3, SLCO1B1, TPMT, UGT1A1, VKORC1), associated to different drug metabolizing rates, were characterized by genotyping using a genome wide commercial array. Widely used drugs such as anti-coagulant warfarin and lipid lowering agent atorvastatin were associated to an alarmingly high percentage of users with intermediate/poor metabolism for them. Significant differences in the frequency of normal/intermediate/poor/ultrarapid/rapid metabolizers were observed for CYPD26 (p<0.001), CYP2C19 (p<0.001) and UGT1A1 (p<0.001) between the Czech and the Finnish study populations. Our study demonstrated that administration of some popular drugs to a Czech random sample population is associated with different drug metabolizing rates and therefore exposing to risk for ADRs. We also highlight interethnic differentiation of some common pharmacogenetics variants between Central (Czech) and North European (Finnish) population studies, suggesting the utility of PGx-informed prescription based on variant genotyping.

• MeSH
• cytochrom P-450 CYP2D6 genetika   MeSH
• cytochrom P450 CYP2C19 genetika   metabolismus   MeSH
• cytochrom P450 CYP2C9 genetika   metabolismus   MeSH
• epoxidreduktasy vitaminu K genetika   MeSH
• farmakogenetika * MeSH
• genotyp MeSH
• lidé MeSH
• polymorfismus genetický * MeSH
• polypeptid C přenášející organické anionty genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

Acid-β-glucosidase (GCase, EC3.2.1.45), the lysosomal enzyme which hydrolyzes the simple glycosphingolipid, glucosylceramide (GlcCer), is encoded by the GBA1 gene. Biallelic mutations in GBA1 cause the human inherited metabolic disorder, Gaucher disease (GD), in which GlcCer accumulates, while heterozygous GBA1 mutations are the highest genetic risk factor for Parkinson's disease (PD). Recombinant GCase (e.g., Cerezyme® ) is produced for use in enzyme replacement therapy for GD and is largely successful in relieving disease symptoms, except for the neurological symptoms observed in a subset of patients. As a first step toward developing an alternative to the recombinant human enzymes used to treat GD, we applied the PROSS stability-design algorithm to generate GCase variants with enhanced stability. One of the designs, containing 55 mutations compared to wild-type human GCase, exhibits improved secretion and thermal stability. Furthermore, the design has higher enzymatic activity than the clinically used human enzyme when incorporated into an AAV vector, resulting in a larger decrease in the accumulation of lipid substrates in cultured cells. Based on stability-design calculations, we also developed a machine learning-based approach to distinguish benign from deleterious (i.e., disease-causing) GBA1 mutations. This approach gave remarkably accurate predictions of the enzymatic activity of single-nucleotide polymorphisms in the GBA1 gene that are not currently associated with GD or PD. This latter approach could be applied to other diseases to determine risk factors in patients carrying rare mutations.

• MeSH
• celulasy * genetika   MeSH
• Gaucherova nemoc * farmakoterapie   genetika   MeSH
• heterozygot MeSH
• lidé MeSH
• mutace MeSH
• Parkinsonova nemoc * genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVE: The aim of the study was to evaluate the variant (rs2910829) of the PDE4D gene in relation to its influence on biochemical, anthropometric and physiological parameters in patients with coronary artery disease and healthy subjects of the Eastern Slovak population. METHODS: The male group consisted of 72 individuals and the female group consisted of 132 individuals. On the basis of clinical screening the subjects were divided into two groups - with ischaemic heart disease and control group. Genomic DNA was isolated from peripheral blood using a commercial NucleoSpin® Blood Machenery-Nagel kit. Molecular genetic analysis of the polymorphism under study was performed using the StepOneTM Real-Time PCR System instrument. The lipid profile markers TC, HDL, LDL, TG were measured by Cobas Integra 400 plus biochemical analyser, and systolic and diastolic blood pressure using a digital blood pressure monitor. Among anthropometric parameters, body height and weight, waist and hip circumference were measured and BMI and WHR indices were calculated. RESULTS: A statistically significant (p = 0.018) possible association between the mutant T allele and ischaemic heart disease was found in men. In women, we found a statistically significant difference in the systolic (p = 0.013) and diastolic blood parameters (p = 0.005) in the CC genotype. In the group of women, we found statistically significant differences in all observed anthropometric parameters and in LDL and TC markers. In the group of men divided on the basis of BMI, statistical significance was found in systolic blood pressure (p = 0.028). In the group of women with ischaemic heart disease, we found a negative correlation between BMI and HDL. CONCLUSION: The study contributes to new findings of the representation of genotypes and alleles of the rs2910829 PDE4D gene polymorphism in the Slovak population. This is a pilot study. Interactions between genotype and observed anthropometric, physiological and biochemical markers were confirmed.

• MeSH
• antropometrie MeSH
• cyklické nukleotidfosfodiesterasy, typ 4 genetika   MeSH
• index tělesné hmotnosti MeSH
• ischemická choroba srdeční * genetika   MeSH
• lidé MeSH
• nemoci koronárních tepen * MeSH
• pilotní projekty MeSH
• rizikové faktory MeSH
• tělesná výška MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: The primary objective was to comprehensively assess the association between single nucleotide polymorphisms (rs562556 and rs2479409) in the PCSK9 gene with biochemical parameters - C-reactive protein (CRP), glucose (GLU), triglyceride (TAG), low-density lipoprotein cholesterol (LDL CHOL), non-high-density lipoprotein cholesterol (non HDL CHOL), high-density lipoprotein cholesterol (HDL CHOL), cholesterol (CHOL), and anthropometric parameters (visceral fat), overweight/obesity and cardiovascular risk. METHODS: A total of 71 women aged 23-64 years were divided into three groups based on body mass index (BMI). BMI ≥ 25/≥ 30 kg/m2 was the criterion for assessment of overweight/obesity. Anthropometric, biochemical and genetic examinations were performed on the probands. Changes in markers in each group and their association with cardiovascular risk were monitored. RESULTS: We can conclude that in our study population we observed differences between the BMI categories for biochemical markers (CRP, LDL CHOL, non HDL CHOL, HDL CHOL, LDL CHOL) and anthropometric marker (visceral fat). Atherogenic index of plasma (AIP), Castelli's Risk Index I (CRI-I) and atherogenic coefficient (AC) confirmed high cardiovascular risk for the obese women category (0.045); (< 0.013); (< 0.010). Genotype and allele frequencies for the PCSK9 gene in the overweight and obese groups showed higher allele frequencies of allele A for both polymorphisms of the gene. CONCLUSIONS: PCSK9 gene expression is associated with biological processes such as lipid metabolism and inflammation. Cholesterol-lowering therapies are the gold standard for reducing the risk of cardiovascular mortality and morbidity. Administration of monoclonal antibodies (mAbs) against PCSK9 is a novel lipid-lowering therapeutic approach in adults to reduce the risk of cardiovascular disease.

• MeSH
• cholesterol MeSH
• dospělí MeSH
• kardiovaskulární nemoci * MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• nadváha * epidemiologie   MeSH
• obezita genetika   MeSH
• proproteinkonvertasa subtilisin/kexin typu 9 genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVES: Diabetes mellitus type 2 (T2DM) is a multifactorial and polygenic disorder characterised by chronic hyperglycaemia accompanied by impaired lipid, carbohydrate, and protein metabolism. The disease is associated with several genetic polymorphisms, including the FokI polymorphism in the vitamin D receptor (VDR) gene. METHODS: We conducted a study of 327 probands (191 T2DM patients, 136 controls), with a mean age 65.06 (SD ± 10.88) years of patients with T2DM and 58.89 (SD ± 6.59) years in the healthy probands. We investigated the association between FokI polymorphism and biochemical parameters in T2DM patients in the Slovak population. Anthropometric measurements, biochemical, and genetic analysis were statistically evaluated by Statistica ver.13 software using t-tests. RESULTS: Biochemical analysis confirmed significantly higher mean values of total cholesterol (TC), triglyceride (TG), glucose (GLU), and uric acid (UA) (p < 0.001) in T2DM probands and statistically significantly lower values of high-density lipoprotein (HDL), cholesterol and vitamin D (p < 0.001). Allele frequencies and genotype distributions of the FokI (rs2228570) polymorphism were not significantly different between T2DM patients and controls (p = 0.909). Patients with T2DM and TT genotype had the highest glucose level of 11.39 (SD ± 2.32) uU/ml (p < 0.001). CONCLUSION: Our study did not provide evidence for an association of the investigated FokI polymorphism of the VDR gene with T2DM in the Slovak population. Further research is needed to evaluate the impact of single nucleotide polymorphisms (SNPs) in the VDR gene, focusing on related genetic analyses in a larger T2DM cohort.

• MeSH
• cholesterol MeSH
• diabetes mellitus 2. typu * komplikace   MeSH
• genetická predispozice k nemoci MeSH
• genotyp MeSH
• glukosa MeSH
• jednonukleotidový polymorfismus MeSH
• lidé MeSH
• receptory kalcitriolu * genetika   metabolismus   MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• Check Tag
• lidé MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH