Jarmila Bernasovská

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. Following a number of anthropometric measurements, the FTO rs9939609 polymorphism was genotyped in 312 Roma/Gypsy individuals. We observed significant differences in body mass index (BMI), waist circumference, and waist-to-hip ratio between different genotypes (P = 0.003, P = 0.012, and P = 0.03, respectively). The waist circumference in the subjects with AA genotype was about 7.1 cm larger than in those with TT genotypes (P = 0.005). However, the strongest association of minor allele A of the rs9939609 FTO polymorphism was found with BMI (odds ratio, 1.55; 95% confidence interval, 1.129-2.128; P = 0.007), even after adjusting for age, sex, and smoking status. This study provides the first report of allele and genotype frequencies for the rs9939609 polymorphism and also the first evidence of the association of the FTO variant with obesity in the Roma/Gypsy population.

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 purpose of this study was to compare the accuracy of three types of Y-haplogroup prediction software and to determine the structure of Slovak population revealed by the Y-chromosome haplogroups. We used a sample of 166 Slovak males in which 12 Y-STR markers were genotyped in our previous study. These results were analyzed by three different software products that predict Y-haplogroups. To estimate the accuracy of these prediction software, Y-haplogroups were determined in the same sample by genotyping Y-chromosome SNPs. Haplogroups were correctly predicted in 98.80% (Whit Atheys Haplogroup Predictor), 97.59% (Jim Cullens Haplogroup Predictor) and 98.19% (YPredictor by Vadim Urasin 1.5.0) of individuals. The occurrence of errors in Y-chromosome haplogroup prediction suggests that the validation using SNP analysis is appropriate when high accuracy is required. The results of SNP based haplotype determination indicate that 39.15% of the Slovak population belongs to R1a-M198 lineage, which is one of the main European lineages.

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 0.9982. Pairwise haplotype distances showed that the Eastern Slovak Caucasian population is not significantly different from the Slavs populations and is separated from the Balkan nations and the German speaking populations.

Genetic variation analysis of 15 autosomal STR loci in Eastern Slovak Caucasian and Romany (Gypsy) population

The genotype polymorphism studies were carried out on two different populations: Eastern Slovak Caucasian (138) and Romany (Gypsy) (138), both from the town of Presov, at 15 highly polymorphic short tandem repeats (STRs) loci. The selected kit PowerPlex 16 system (Promega) included amelogenin, two penta-nucleotide repeats and 13 tetra-nucleotide repeats. The comparison of the allele frequencies between Eastern Slovak Caucasians and Romanies has shown significant differences in the majority of the focused loci. The P-values of exact test for Hardy-Weinberg equilibrium probabilities, observed and expected heterozygosity, matching probability, power of discrimination and exclusion, polymorphic information content, typical paternity index, genetic diversity and the other population-genetic indices were calculated.

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. Genomic DNA was extracted and purified from peripheral blood leukocytes by the commercial kit JetQuick (Genomed GmbH, Germany) using a standard protocol. Genotyping was performed using the Custom TaqMan® SNP Genotyping Assays. The lumbar L1–L4 spine BMD (g/cm2) and T-score in the subgroup of Slovak postmenopausal women with osteoporotic fractures were significantly lower than those in the subgroup of women without fracture (p = 0.0025; p = 0.0009). We identified the T245G (rs3134069) polymorphism in the TNFRSF11B gene associated with osteoporotic fractures (vertebral fractures: p = 0.0320; non-vertebral fractures: p = 0.0005; all fractures: 0.0000). The polymorphism T245G (rs3134069) in the TNFRSF11B gene could be used together with other genetic markers to identify individuals at high risk of osteoporotic fractures. The results from the present study provided more evidence to reveal the role of TNFRSF11B gene polymorphisms in BMD and the risk of osteoporotic fractures.

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 (4.90%), while the frequency of H63D mutation (4.09%) is lower than any reported in Europe so far. S65C mutation was not present in the cohort. These mutation frequencies can be explained rather by gene influx and genetic isolation than by genetic inheritance from a former Roma/Gypsy homeland.

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 10.72% between populations (Fst = 0.1027; p = 0.0000). The haplotype diversities were ranging from 0.9258 to 0.9978, and indicated a high potential for differentiating between male individuals. The study reports differences in allele frequencies between the Romanies, Habans and Slovak Caucasian men. Selected loci showed that both the Romany and Haban population belonged to endogamous and relatively small founder population groups, which developed in relatively reproductive isolated groups surrounded by the Slovak Caucasian population.

Ethnic Differences in the Association of Thrombophilic Polymorphisms with Obstetric Complications in Slovak and Roma (Gypsy) Populations

AIMS Hereditary as well as acquired thrombophilia is associated with a higher incidence of severe obstetric complications such as preeclampsia, spontaneous pregnancy loss, placental abruption, and fetal growth retardation. The aim of our study was to examine the association of selected thrombophilic polymorphisms (factor V Leiden, MTHFR C677T, and MTHFR A1298C) with pregnancy complications in the Slovak majority population and the Roma (Gypsy) ethnic population. The study included 354 women; 120 patients and 105 controls from the Slovak majority population, 50 patients and 79 controls from the Slovak Roma population. Genotyping was performed by the real-time polymerase chain reaction method using TaqMan(®) MGB probes. RESULTS A statistically significant higher frequency of factor V Leiden (p=0.001, odds ratio [OR]=5.9) and MTHFR C677T polymorphism (p=0.011, OR=1.7) was observed in the Slovak majority patient group compared to the control group. The incidence of MTHFR A1298C polymorphism between patients and controls did not differ significantly. None of the three polymorphisms studied was in association with pregnancy complications in the group of Roma women. CONCLUSIONS Our study has confirmed the variable distribution of selected thrombophilic polymorphisms in different ethnic groups as well as their various effects on the clinical phenotype.

Analysis of SCN5A Gene Variants in East Slovak Patients with Cardiomyopathy

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. The SCN5A gene mutations are found in approximately 2% of patients with dilated cardiomyopathy (DCM), and they may be potential phenotype modifiers in hypertrophic cardiomyopathy (HCM). The role of SCN5A gene mutations in cardiomyopathy is not fully elucidated.

Heterochromatin Variants in Slovak Women with Reproductive Failure

Abstract Various studies have reported a higher incidence of heterochromatin variants among individuals with idiopathic reproductive failure. The aim of the present study was to assess the frequency of chromosomal heteromorphisms in 948 women with history of reproductive failure and 478 controls in the Presov region (Slovakia) (1998-2013) using G-banding and C-banding cytogenetic techniques. In 95 individuals (10.02%) with reproductive failure heterochromatin variants of chromosomes 1, 9, 16 and Y were detected. In the control group, there were 15 (3.15%) heterochromatin variants. The most frequent heterochromatin variants in the reproductive failure group were heterochromatin variants within chromosome 9 (9qh+/9qh-/inv(9)). The overall incidence of heterochromatin variants in women with reproductive failure was higher than in controls (p<0.0001; 95% CI 1.971-5.996). The results of the study confirmed the higher occurrence of chromosome anomalies in Slovak women with reproductive failure that absolutely reasons indication of cytogenetic examination.