PCSK9 and Lipid Metabolism: Genetic Variants, Current Therapies, and Cardiovascular Outcomes.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a crucial role in the modulation of lipid metabolism as a critical negative regulator of hepatic low-density lipoprotein receptor (LDLR) levels and circulating low-density lipoprotein (LDL) clearance. Numerous gain-of-function (GOF) mutations in PCSK9 have been identified as causing familial hypercholesterolemia (FH) by reducing LDLR levels, and loss-of-function (LOF) mutations associated with a hypercholesterolemia phenotype protective against atherosclerosis. PCSK9 represents an example of successful translational research resulting in the identification of PCSK9 as a major drug target for a lipid-lowering therapy.

Porotic hyperostosis and cribra orbitalia in samples from the Late Hillfort Period sites at Dětkovice - Za zahradama (district Prostějov) and Vídeňská street (district Brno), Czech Republic.

Porotic hyperostosis and cribra orbitalia are pathological changes occurring on the human skull. These changes were observed and evaluated on skeletal remains from Dětkovice - Za zahradama and Vídeňská Street in Brno; both sites are dated back to the 10 to 12 centuries AD. A total of 605 subjects were assessed for age, sex, and the above-stated pathologies using standard methods.

Evaluation of COLIA1 gene rs1107946 polymorphism in relation to bone mineral density and fracture risk in Slovak postmenopausal women.

Objectives: The aim of the study was the evaluation of the rs1107946 polymorphism of the COLIA1 gene impact on bone mineral density and fracture risk in Slovak postmenopausal women.

Methods: One hundred and twenty-seven postmenopausal Slovak women with a diagnosis of osteopenia/osteoporosis were genotyped for rs1107946 polymorphism of the COLIA1 gene. Clinical and anthropometric data were obtained.

Anthropological analysis of skeletal remains from the site Vyšná Myšľa - Koscelek.

The archaeological site Vyšná Myšľa - Koscelek is located in the southeast of the Slovak Republic, and it is peculiar by its location in the middle of the woods near a thermal spring. Burials could be dated to the 13 to 14 centuries based on the presence of the ruins of the church, albeit the funeral practices could last until the 18 century. A total of 53 individuals were examined, in whom the age at death, sex and stature were morphoscopically and metric estimated by standard anthropological methods, and the presence of non-metric traits and pathological conditions was also recorded.

Ankylosing spondylitis on unidentified individual from early modern times found in reformed church (Silická Brezová, Slovakia): a case-based review.

The grave situated in the central part of the reformed church in Silická Brezová in Slovakia contained the human skeletal remains of one individual. The aim of this study was to confirm the presence of ankylosing spondylitis on these skeletal remains. Determine the sex, age at death, stature, and ancestry of the individual by anthropological methods, and also record and identify other pathological manifestations of diseases.

Oral health status of 6- and 12-year-old children of Roma origin from Eastern Slovakia: a pilot study.

Objective: The purpose of this study was to determine the prevalence and clinical effect of untreated dental caries in Roma children from eastern Slovakia using dmft/DMFT index and SiC index, association between dental caries development and oral hygiene, dietary habits and preventive dental care.

Methods: Dental caries were assessed by recording the dmft index (for primary dentition) and the DMFT index (for permanent dentition) that are used to assess the state of teeth, which expresses the current state of teeth or its development in an individual or the entire population. The SiC index was calculated as the mean dmft of one-third of the population with highest caries scores.

Association between vitamin D receptor gene polymorphisms () and bone mineral density in Slovak postmenopausal women.

Osteoporosis is a skeletal disorder characterized by low bone mass and microarchitectural deterioration of bone tissue with consequent increase in bone fragility and fracture risk. Bone mineral density (BMD), the major determinant of osteoporotic fracture risk, has a particular genetic background. Vitamin D receptor (VDR) is implicated in the regulation of bone mineral density.

Finding the candidate sequence variants for diagnosis of hypertrophic cardiomyopathy in East Slovak patients.

Background: Hypertrophic cardiomyopathy is a heterogeneous myocardial disease. Mutations appearing in several genes might be a potential cause of the disease. The aim of the study was to analyze selected exons of the sarcomeric and non-sarcomeric genes, with the purpose to identify potential candidate genetic variants and to understand etiopathogenetic mechanisms of hypertrophic cardiomyopathy in East Slovak patients.

Analysis of selected genes associated with cardiomyopathy by next-generation sequencing.

Background: As the leading cause of congestive heart failure, cardiomyopathy represents a heterogenous group of heart muscle disorders. Despite considerable progress being made in the genetic diagnosis of cardiomyopathy by detection of the mutations in the most prevalent cardiomyopathy genes, the cause remains unsolved in many patients. High-throughput mutation screening in the disease genes for cardiomyopathy is now possible because of using target enrichment followed by next-generation sequencing.

Relationship between A163G osteoprotegerin gene polymorphism and other osteoporosis parameters in Roma and non-Roma postmenopausal women in eastern Slovakia.

Background: The study was focused on evaluating the possible correlation between biochemical, anthropometric, and genetic indicators of osteoporosis in postmenopausal women. The frequency of genotypes and differences in measured parameters were evaluated within two ethnically different groups of women in Slovakia.

Methods: The study included 310 postmenopausal women divided into non-Roma and Roma groups.

Analysis of SCN5A Gene Variants in East Slovak Patients with Cardiomyopathy.

Objective: Mutations in ion channels genes are potential cause of cardiomyopathy. The SCN5A gene (sodium channel, voltage gated, type V alpha subunit gene; 3p21) belongs to the family of cardiac sodium channel genes. Mutations in SCN5A gene lead to decreased Na+ current and ion unbalance.

TNFRSF11B gene polymorphisms, bone mineral density, and fractures in Slovak postmenopausal women.

Osteoporosis is a common disease that is characterized by low bone mineral density (BMD), deterioration in bone microarchitecture, and increased fracture risk. Due to its important role in bone biology, the TNFRSF11B gene, coding for OPG, has been considered as a candidate gene for osteoporosis. In this study, single nucleotide polymorphisms (SNPs) A163G, T245G, and G1181C (rs3102735, rs3134069, and rs2073618, respectively) within the TNFRSF11B gene were studied for association with BMD and fracture incidence in a cohort of 327 postmenopausal Slovak women.

Y-SNP analysis versus Y-haplogroup predictor in the Slovak population.

Human Y-chromosome haplogroups are important markers used mainly in population genetic studies. The haplogroups are defined by several SNPs according to the phylogeny and international nomenclature. The alternative method to estimate the Y-chromosome haplogroups is to predict Y-chromosome haplotypes from a set of Y-STR markers using software for Y-haplogroup prediction.

The frequency of factor V Leiden and prothrombin G20210A mutations in Slovak and Roma (Gypsy) ethnic group of Eastern Slovakia.

Factor V Leiden and prothrombin G20210A are the two most prevalent causes of inherited thrombophilia. The prevalence of these mutations varies widely in healthy Caucasian population. The aim of our study was to determine the frequency of factor V Leiden and prothrombin G20210A mutations in Slovak and Roma ethnic group from Eastern Slovakia.

Unique frequencies of HFE gene variants in Roma/Gypsies.

The aim of this study was to assess the frequencies of three hemochromatosis gene (HFE) mutations in ethnic Roma/Gypsies in Slovakia. A cohort of 367 individuals representing general population and not preselected for health status was genotyped by TaqMan real-time PCR assay for C282Y, H63D and S65C mutations in HFE gene. A unique genetic profile was revealed: C282Y is found in the highest frequency of all Central European countries (4.

Association of the FTO rs9939609 polymorphism with obesity in Roma/Gypsy population.

The rs9939609 SNP located in the first intron of the fat mass and obesity associated gene (FTO) has been found to be associated with common obesity mainly in populations of European descent. The Roma/Gypsy population as an ethnic minority of Asian Indian origin is well known for its adverse health status with a high prevalence of obesity. The main aim of this study was to examine the contribution of the rs9939609 FTO polymorphism to the high prevalence of obesity in the Roma/Gypsy population.

Incidence of microdeletions in the AZF region of the Y chromosome in Slovak patients with azoospermia.

Aims: The Y chromosome accumulates male-related genes including sex-determining region of Y-chromosome (SRY) and several spermatogenesis-related genes. The long arm contains azoospermia factor (AZF) region (including sub-regions AZFa, AZFb and AZFc). Microdeletions in this region are responsible for azoospermia and oligospermia and result in the male infertility.

Allele frequencies and population data for 11 Y-chromosome STRs in samples from Eastern Slovakia.

Haplotype data of 11 Y-STR loci (DYS391, DYS389I, DYS439, DYS389II, DYS438, DYS437, DYS19, DYS392, DYS393, DYS390 and DYS385) was obtained from 629 Slovak Caucasian men living in Eastern Slovakia. A total of 474 haplotypes were identified, of which 395 were unique. The haplotype diversity value was 0.

Comparison of Y-STR polymorphisms in three different Slovak population groups.

Eleven Y-chromosomal microsatellite loci included in the Powerplex Y multiplex kit were analyzed in different Slovak population samples: Habans (n = 39), Romanies (n = 100) and Slovak Caucasian (n = 148) individuals, respectively, from different regions of Slovakia. The analysis of molecular variance between populations indicated that 89.27% of the haplotypic variations were found within populations and only 10.