Распределение вариантов однонуклеотидного полиморфизма rs6795970 гена SCN10A среди молодого населения Республики Молдова

Distribuția variantelor polimorfismului de un singur nucleotid rs6795970 al genei SCN10A la populația tânără din Republica MoldovaBackground. PR interval reflects atrial and atrioventricular nodal conduction time and is an important determinant of arrhythmia risk. Genome-wide association studies (GWAS) have identified association of nonsynonymous SNP, rs6795970, in the SCN10A gene with PR interval in individuals of European ancestry. Purpose. To estimate the distribution of rs6795970 variants, associated with PR interval in young population of Republic of Moldova. Methods. 1390 young participants from Republic of Moldova with age range: 19-25 years, were genotyped for rs6795970 in the SCN10A gene, using TaqMan technology. Results. The genotype A/A, A/G, G/G distributions of rs6795970 among the young participants were 15%, 48%, 37% respectively (χ2 = 0.161, p = 0.688). The allele frequencies for A and G in young participants were 39% and 61% respectively. Conclusion. The minor allele frequency (MAF) in young Moldavian population was 0.39 for rs679570 and was consistent with 1000 Genomes Project data in the European population – 0.41. 15% of all participants (the AA genotype), may have an increased risk of conduction abnormalities.Распределение вариантов однонуклеотидного полиморфизма rs6795970 гена SCN10A среди молодого населения Республики Молдов

Prevalence of 35delG mutation in GJB2 gene in the Moldovan population

Laboratory of Genetics, Center for Drug Research, Nicolae Testemitanu State University of Medicine and Pharmacy, Chisinau, the Republic of Moldova, Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania. The 75th anniversary of Nicolae Testemitanu State University of Medicine and Pharmacy of the Republic of Moldova (1945-2020)Background: Guanine deletion 35delG in GJB2 exon 2 is the pathogenic mutation responsible for up to 70% of cases of congenital non-syndromic sensorineural hearing loss (NSHL) among Europeans. The early molecular diagnostic of hearing loss nature has become important while considering the cochlear implants. The purpose of this study was to establish the frequency of 35delG deletion in GJB2 gene among patients with severe NSHL and its prevalence among Moldovan residents with normal hearing. Material and methods: 40 patients with congenital bilateral profound NSHL and 300 individuals with normal hearing were examined for deletion 35delG, by using Custom TaqMan SNP genotyping Assay. Results: 12 (30%) patients with homozygous genotype for 35delG mutation were identified, whereas 8 patients (20%) were heterozygous. The study reported 4 (1.33%) carriers of 35delG mutation among 300 Moldovan individuals with normal hearing. Conclusions: The present study results suggest a need for including the 35delG molecular testing into the national program of neonatal screening of hearing loss. Considerations on the genetic carrier testing should be made in genetic counseling and family planning

Ponderea unor profiluri ale metilării promotorului genei p15 (locus: CDKN2B) la pacienții cu cardiopatie ischemică de origine aterosclerotică

Studiul a avut ca scop stabilirea ponderii unor profiluri ale metilării promotorului genei p15 (locus CDKN2B) în celulele sanguine ale pacienților cu cardiopatie ischemică de origine aterosclerotică prin amplifi carea porţiunilor genice cu ajutorul perechilor de praimeri nonmetil-specifici şi metil-specifici (tehnica MSP). Obiectul studiului l-au constituit 35 de pacienţi și 35 persoane sănătoase. Concluziile: 1) A fost stabilită corespunderea fenotipului cardiopatie ischemică cu metilarea ADN, la nivelul promotorului genei p15 (profilul MM); 2) Celulele analizate UM, au reprezentat un amestec, în care, cele mai multe au conținut ambele molecule de ADN metilate (MM), iar un număr mai mic de celule au inclus fie ambele molecule de ADN nemetilate (UU), fie o moleculă ADN metilată, iar cealaltă – nemetilată (UM)

Silent cardiovascular risk factors among medical students

Discipline of Internal Medicine-Semiology, Department of Internal Medicine, Laboratory of Genetics, Nicolae Testemitanu State University of Medicine and Pharmacy Chisinau, the Republic of MoldovaAbstract. Background: Dyslipidaemia and obesity are recognized modifiable cardiovascular risk factors, a major health challenge of the 21st century. Youth obesity and lipid abnormalities are insufficiently documented. Asymptomatic young people tend not to appeal to health services, but they may be at high cardiovascular risk. Material and methods: A cross-sectional study was performed on 138 male medical students. All the participants underwent the anthropometric and clinical examination. The obtained data were statistically processed by using the “Statistica 6.0” software program. The difference was considered statistically significant with p <0.05. Results: It was established that 34.1% of respondents had excessive fat accumulation, 5.1% were defined as obese, according to BMI criteria. According to ethnic- and sex-specific WC cut-offs, 14.5% of subjects were centrally obese. Out of the cohort of medical students, 34% had at least one abnormal lipid parameter. The low HDLc was the most prevalent dyslipidemia in all the students – 12.3%. The results of the survey showed that rural young males were more likely to manifest lipid abnormality – 38.3% versus 22.8% for the urban areas, also rural origin was associated with a higher rate of central obesity – 16%. Conclusions: Young men from Moldova have an alarming rate of asymptomatic dyslipidemia and obesity. Our findings support the need for early general preventive efforts targeting the young population at high risk

Distribution of rs6795970 SNP variants in SCN10A gene in young population of the Republic of Moldova.

Background. PR interval reflects atrial and atrioventricular nodal conduction time and is an important determinant of arrhythmia risk. Genome-wide association studies (GWAS) have identified association of nonsynonymous SNP, rs6795970, in the SCN10A gene with PR interval in individuals of European ancestry. Purpose. To estimate the distribution of rs6795970 variants, associated with PR interval in young population of Republic of Moldova. Methods. 1390 young participants from Republic of Moldova with age range: 19-25 years, were genotyped for rs6795970 in the SCN10A gene, using TaqMan technology. Results. The genotype A/A, A/G, G/G distributions of rs6795970 among the young participants were 15%, 48%, 37% respectively (χ2 = 0.161, p = 0.688). The allele frequencies for A and G in young participants were 39% and 61% respectively. Conclusion. The minor allele frequency (MAF) in young Moldavian population was 0.39 for rs679570 and was consistent with 1000 Genomes Project data in the European population – 0.41. 15% of all participants (the AA genotype), may have an increased risk of conduction abnormalities

Variația genetică a genei SCN10A în populația tânără din Republica Moldova

Background. PR interval reflects atrial and atrioventricular nodal conduction time, and is an important determinant of arrhythmia risk. Genome-wide association studies (GWAS) have identified association of a nonsynonymous SNP, rs6795970, in the SCN10A gene with PR interval in individuals of European ancestry. Objective of the study. Determine distribution of the genetic variants of rs6795970, associated with PR interval in young population of Republic of Moldova. Material and Methods. 1390 young participants from Republic of Moldova with age range: 19-25 years, were genotyped for rs6795970 in the SCN10A gene, using TaqMan SNP Genotyping Assay. Results. The genotype A/A, A/G, G/G distributions of rs6795970 among the young participants were 15%, 48%, 37% respectively (χ2 = 0.161, p = 0.688). The allele frequencies for A and G in young participants were 39% and 61% respectively. Conclusion. The minor allele frequency (MAF) in young Moldavian population was 0.39 for rs6795970 and was consistent with Project 1000Genomes data in the European population – 0.41. The risk allele (A allele) is associated with a predisposition to appear of arrhythmias. Introducere. Intervalul PR reflectă timpul de conducere nodală atrială și atrioventriculară și este un predictor important al riscului de aritmie. Prin studiile de tip GWAS a fost identificată asocierea SNPului rs6795970, nonsinonim, al genei SCN10A, cu intervalul PR la indivizii din populația europeană. Scopul lucrării. Determinarea distribuției variantei genetice a polimorfismului rs6795970 asociat cu intervalul PR în populația tânără din Republica Moldova. Material și Metode. Genotiparea polimorfismului rs6795970 al genei SCN10A la 1390 de participanți tineri din Republica Moldova, cu vârste cuprinse între 19-25 de ani, s-a efectuat prin tehnica TaqMan SNP Genotyping Assay. Rezultate. S-a stabilit că distribuțiile genotipurilor A/A, A/G, G/G pentru rs6795970 între participanți tineri au fost 15%, 48% și, respectiv, 37% (χ2 = 0,161, p = 0,688). Frecvența alelei A a fost de 39%, iar a alelei majore G de 61%. Concluzii. Frecvența de 0,39 a alelei minore (MAF) în populația tânără din Republica Moldova, pentru rs6795970 este în concordanță cu datele Proiectului 1000Genomes pentru populația europeană – 0,41, ceea ce indică că alela A (alela de risc) este asociată cu predispoziția la apariția aritmiilo

Genetic variation of the SCN10A gene in young population of Republic of Moldova

Laboratory of genetics, State University of Medicine and Pharmacy "Nicolae Testemiteanu" Chișinău, Republic of Moldova, Congresul consacrat aniversării a 75-a de la fondarea Universității de Stat de Medicină și Farmacie „Nicolae Testemițanu” din Republica Moldova, Ziua internațională a științei pentru pace și dezvoltareIntroduction: The electrocardiogram (ECG) is a valuable clinical tool for assessing the function of the cardiac conduction system. The electrocardiographic PR interval represents conduction through the atria and atrioventricular (AV) node to the Purkinje fibers. Delayed conduction in the above parts of the cardiac conduction system, results in prolongation of this ECG parameter. Prolongation of the PR interval leads to increased risk of atrial fibrillation, heart block, and mortality. The duration of the PR interval has an important heritable component, with heritability estimates ranging up to 50% in populations of European and Asian ancestry . Genome-Wide Association studies (GWAS) have identified a common loci associated with PR interval duration. The strongest association was observed between nonsynonymous single nucleotide polymorphism, rs6795970 (G > A), in the SCN10A gene and the PR interval . The SCN10A gene is mapped to chromosome 3p22.2 and encodes the alpha subunit, type X, of a voltage-gated sodium channel. The SCN10A gene is expressed in the dorsal root ganglion (DRG), nociceptive nerve fibers, retina, in the myocardium and preferentially in the Purkinje fibers of the cardiac conduction system. The allele A of the SCN10A gene polymorphism (rs6795970) was associated with increased risk of first-degree heart block, bundle-branch block, bifascicular heart block, idiopathic sick sinus syndrome [1-5]. Purpose. Determine distribution of the genetic variants of rs6795970, associated with PR interval in young population of Republic of Moldova. Material and methods: 1390 students from Nicolae Testemitsanu State University of Medicine and Pharmacy, aged between 19-25 years, enrolled in our cross-sectional study. Written informed consent was obtained from all the participants. Personal identifiers associated with medical information and blood samples were encrypted with a special codification and then analyzed. The study was approved by the Nicolae Testemitsanu SUMPh Research Ethics Committee. Genomic DNA was isolated from buffy coat using silica-based membrane technology in the form of a spin column Gene JET Genomic DNA Purification Kit (Thermo Scientific, USA) according to the manufacturer’s protocol. Genotype analysis of all 1390 participants to detect rs6795970 (G > A) in the SCN10A gene was performed with commercially available TaqMan assay kit (Assay ID: C__29261054_10) on a QuantStudio 6 Flex instrument (Thermo Fisher Scientific). The differences of genotype frequencies of the rs6795970 have been analyzed by the chi-square Test (χ2), also used to test deviations of genotype distribution from the Hardy-Weinberg equilibrium. Results: Out of 1390 samples, the genotyping successful call rate was 99.7%. The validity of the genotyping results is in concordance with the allele frequency distribution predicted by Hardy-Weinberg equilibrium for rs6795970 (χ2 = 0.161, p = 0.688). The distribution of genotypes and allele frequencies of the rs6795970 in the sample tested is shown in table 1. Conclusions: In this study, we determined that distribution of the genetic variants of rs6795970, associated with PR interval in young population of Republic of Moldova was consistent with 1000 Genomes data in the European population. Thus, our data demonstrate that at least 15% of all participants (the AA genotype), may have an increased risk of conduction abnormalities

Estimarea indicelui de aterogenitate a plasmei în rândul studenților medici

Background. Cardiovascular disease (CVD) has become a global public health concern. A precise and quick recognition of susceptible individuals to develop CVD is imperative to reduce its burden. Atherogenic index of plasma (AIP) is a logarithmically transformed ratio of molar concentrations of triglycerides to HDL-cholesterol, being affordable, specific, and useful tool to predict cardiovascular events. Objective of the study. Studying the distribution of atherogenic index of plasma in young medical student cohort. Material and Methods. A cross-sectional study was performed including 440 healthy students (18-30y). Anthropometric and clinical measurements were acquired from all enrolled individuals. Also, a blood sample of each participant was obtained to complete biochemical analyses (triglycerides, total cholesterol, LDL cholesterol, and HDL cholesterol. Finally, atherogenic index of plasma was estimated. Results. The mean AIP was significantly higher in young males 0.08 ± 0.1, than in females (0.05± 0.1, p=0.016). According to AIP category, 285 (64.8%) were in low risk group, 119 (27 %) - intermediate risk and 36 (8.2%) presented high risk of developing CVD. Out of 34.3% centrally obese participants, 32.5% were at intermediate or high risk. Conclusion. The documented rate of students in intermediate and high risk group is alarming. Futher studies are needed to assess the correletion between the atherogenic index of plasma and cardiovascular risk factors in asymptomatic young students, in order to be used as a regular monitoring index of CVD. Introducere. Boala cardiovasculară (BCV) a devenit o problemă de sănătate publică la nivel mondial. Recunoașterea sigură și rapidă a persoanelor susceptibile de a dezvolta BCV este imperativă pentru a reduce povara acesteia. Indicele de aterogenitate a plasmei (IAP) este un raport transformat logaritmic al concentrației molare de trigliceride la HDL-colesterol, fiind un instrument accesibil și util pentru a prezice BCV. Scopul lucrării. Evaluarea distribuției indicelui de aterogenitate a plasmei în cohorta studenților medici. Material și Metode. În studiul de tip transversal, au fost incluși 440 de studenți sănătoși (18-30 de ani). Toți participanții au fost supuși examenului antropometric și clinic. Ulterior, sau recoltat analizele biochimice cu deteminarea următorilor parametri: trigliceride, colesterol total, LDL-colesterol și HDL-colesterol și a fost estimat IAP. Rezultate. Valoarea medie a parametrului IAP a fost semnificativ mai mare la bărbați - 0,08 ± 0,1 decât la femei (0,05± 0,1; p = 0,016). Conform categoriilor IAP, 285 (64,8%) au fost în grupul cu risc scăzut, 119 (27%) - risc intermediar și 36 (8,2%) au prezentat un risc sporit de BCV. În cohorta participanților obezii, la 32,5% s-a inregistrat un risc aterogen intermediar sau sporit. Concluzii. Rata studenților din grupul cu risc intermediar și sporit este alarmantă. Sunt necesare studii suplimentare pentru a determina corelația dintre indicele de aterogenitate a plasmei și factorii de risc cardiovascular la studenții asimptomatici, pentru a implemementa IAP drept instrument de predicție pentru BCV

Utilitatea potenţială a profilurilor metilice ale ADN pentru procesul de promovare a markerilor molecularepigenetici în diagnosticul diferenţial al leucemiilor acute

În cadrul studiului dat au fost obţinute date preliminare privind ponderea grupurilor de pacienţi cu diferite subtipuri de leucemii acute în lotul specifi c de profi l metilic ADN. Am conchis că moleculele nemetilate de ADN, la nivelul promotorului genei p15, prezintă potenţial de marker molecular-epigenetic al leucemiei acute monoblastice la om. Pentru prelucrarea statistică a datelor a fost utilizat testul „U-Fisher”, iar valoarea p≤0,1 a fost interpretată ca tendinţă statistică а diferenţelor dintre grupurile comparate

Endothelial nitric oxide synthase gene polymorphism in patients with acute coronary syndrome

Laboratorul de Genetică USMF „Nicolae Testemiţanu”, IMSP Institutul de CardiologieThe aim was to examine the effect of polymorphism of the endothelial nitric oxide synthase (eNOS) gene, located in the 4a/4b VNTR (variable number of tandem repeats) minisatelit marker of eNOS in patients with acute coronary syndrome. The career of the intron- 4a/4b and 4b/4b polymorphism of the eNOS gene was associated with atherosclerotic coronary lesion and increased risk of myocardial infarction. Larger studies are needed to understand the importance of eNOS gen in the coronary heart disease. Scopul studiului a fost examinarea rolului polimorfismului genei sintetazei endoteliale de oxid nitric (eNOS), localizate pe markerul polimorf minisatelit eNOS-4a/4b VNTR (variable number of tandem repeats) la pacienţii cu sindrom coronarian acut (SCA). Portajul de alelele intron-4a/4b şi 4b/4b VNTR ale eNOS s-a asociat cu lezare aterosclerotică coronariană şi risc crescut de infarct miocardic. Sunt necesare studii largi pentru a înţelege importanţa polimorfismului genei eNOS în boala coronariană