Vaiva Lesauskaite

Associations between apolipoprotein E genotype, diet, body mass index, and serum lipids in Lithuanian adult population.

Background Apolipoprotein E (APOE) polymorphism is associated with lipid levels. Some studies have reported that blood lipid response to diet or obesity varies depending on APOE genotypes. The aim of this study was to assess the effect of APOE genotypes, the intake of saturated fatty acids (SFA), and obesity on serum lipid levels in Lithuanian adult population. Methodology/Principal Findings A cross-sectional health survey was carried out in five municipalities of Lithuania. The random sample was obtained from lists of 25–64 year-old inhabitants registered at primary health care centres. The data from 996 subjects (416 men and 580 women) were analysed in this study. Two single-nucleotide polymorphisms (rs429358 and rs7412) were assessed using a real-time polymerase chain reaction. 24-hour recall and food frequency questionnaire were used for evaluation of dietary habits. Serum lipids were determined using enzymatic methods. Men and women with the APOE2 genotype had the lowest level of total cholesterol (TC) (p = 0.002 for men, and p = 0.02 for women) and low-density lipoprotein cholesterol (LDL-C) (p<0.001). Multivariate linear regression analysis showed that age, genotype APOE2, SFA intake, and body mass index (BMI) were significant determinants of TC and LDL-C level (with p values ranging from 0.043 to 0.001). Our data did not reveal any statistically significant interactions between APOE genotype and SFA intake or between APOE genotype and BMI regarding TC and LDL-C level (all p>0.05). However, the predictive power of the regression model for LDL-C improved when gene-BMI interaction and gene-BMI interaction plus gene-nutrient interaction were added (p = 0.04 and p = 0.032 for R2 change, respectively). Conclusions/Significance APOE genotypes, SFA intake, and obesity were found to be associated with blood lipid levels in Lithuanian adult population. Analysis of gene-diet and gene-obesity interactions did not confirm that the effects of diet and obesity on TC and LDL-C level significantly depended on APOE genotype.

Association between APOE, SCARB1, PPARα polymorphisms and serum lipids in a population of Lithuanian adults

BackgroundDyslipidemia is one of several known risk factors for coronary heart disease, a leading cause of death in Lithuania. Blood lipid levels are influenced by multiple genetic and environmental factors. Epidemiological studies demonstrated the impact of nutrition on lipid levels within the Lithuanian population although the role of genetic factors for dyslipidemias has not yet been studied. The objective of this study was to assess the distribution of the APOE, SCARB1, PPARα genotypes in the Lithuanian adult population and to determine the relationship of these genotypes with dyslipidemia.MethodsA cross-sectional health survey was carried out in a representative random sample of the Lithuanian population aged 25–64 (n=1030). A variety of single-nucleotide polymorphisms (SNPs) of the APOE (rs429358 and rs7412), SCARB1 (rs5888) and PPARα (rs1800206) genes were assessed using real-time polymerase chain reaction. Serum lipids were determined using enzymatic methods.Results/Principal findingsMen and women with the APOE2 genotype had the lowest level of total and low-density lipoprotein cholesterol (LDL-C). Men with the APOE2 genotype had significantly higher levels of triglycerides (TG) than those with the APOE3 genotype. In men, the carriers of the APOE4 genotype had higher odds ratios (OR) of reduced (<1.0 mmol/L) high density lipoprotein cholesterol (HDL-C) levels versus APOE3 carriers (OR=1.98; 95% CI=1.05-3.74). The odds of having elevated (>1.7 mmol/L) TG levels was significantly lower in SCARB1 genotype CT carriers compared to men with the SCARB1 genotype CC (OR=0.50; 95% CI=0.31-0.79). In men, carriers of the PPARα genotype CG had higher OR of elevated TG levels versus carriers of PPARα genotype CC (OR=2.67; 95% CI=1.15-6.16). The odds of having high LDL-C levels were lower in women with the APOE2 genotype as compared to APOE3 genotype carriers (OR=0.35; 95% CI=0.22-0.57).Conclusions/SignificanceOur data suggest a gender difference in the associations between APOE, SCARB1, PPARα genotypes and lipid levels. In men, the APOE4 genotype and PPARα genotype CG were correlated with an atherogenic lipid profile while the SCARB1 genotype CT had an atheroprotective effect. In women, APOE2 carriers had the lowest odds of high LDL-C.

Physical, behavioural and genetic predictors of adult hypertension: the findings of the Kaunas Cardiovascular Risk Cohort study.

Background The roots of adult hypertension go back to childhood. This study aimed to examine the independent effects of physical, behavioural and genetic factors identified in childhood and mid-adulthood for prediction of adult hypertension. Methods The study subjects were participants of the Kaunas Cardiovascular Risk Cohort study started in 1977 (n = 1082, age 12–13 years). In 2012, a total of 507 individuals (63.9% of eligible sample) participated in the 35-year follow-up survey. Health examination involved measurements of blood pressure (BP), anthropometric parameters, and interview about health behaviours. Subjects were genotyped for AGT (M235T), ACE (I/D, rs4340), ADM (rs7129220), and CACNB2 (rs12258967) genes polymorphisms. A genetic risk score was calculated as the sum of the number of risk alleles at each of four single nucleotide polymorphisms. Results AGT TT genotype male carriers had the highest mean values of systolic BP in childhood. In females, ADM genotype AA was associated with the highest values of systolic and diastolic BP, while CACNB2 genotype CC carriers had the highest values of diastolic BP in childhood. Systolic and diastolic BP in childhood, gain in BMI from childhood to adulthood, and risky alcohol consumption predicted hypertension in middle-aged men. In women, genetic risk score together with diastolic BP in childhood and gain in BMI were significant predictors of adult hypertension. The comparison of four nested logistic regression models showed that the prediction of hypertension improved significantly after the addition of BMI gain. Genetic risk score had a relatively weak effect on the improvement of the model performance in women. Conclusions BP in childhood and the gain in BMI from childhood to adulthood were significant predictors of adult hypertension in both genders. Genetic risk score in women and risky alcohol consumption in men were independently related with the risk of adult hypertension.

The Role of Matrix Metalloproteinases Polymorphisms in Age-Related Macular Degeneration

Abstract Background: Matrix metalloproteinases (MMP) are responsible for the degradation of extracellular matrix components and play an important role in the physiological and pathological remodeling of tissues. Purpose: To assess the impact of MMP-2 Rs2285053 (C –> T), MMP-3 Rs3025039 (5A –> 6A), and MMP-9 Rs3918242 (C –> T) single nucleotide polymorphism on the development of early age-related macular degeneration (AMD). Methods: The study group comprised 148 patients with AMD, and the control group enrolled 526 randomly selected persons. The genotyping of MMP-3 Rs3025039, MMP-2 Rs2285053, and MMP-9 Rs3918242 was performed by using the real-time PCR method. Results: The frequency of the MMP-2 (−735) C/T and MMP-3 (−1171) 5A/6A genotypes did not differ significantly between the patients with AMD and the control group, while the MMP-9 (−1562) C/C genotype was more frequently detected in patients with AMD than the control group (73.7% vs. 64.6%, p = 0.048). Logistic regression analysis showed that the MMP-9 (−1562) C/C genotype increased the likelihood of developing early AMD (OR = 1.51, 95% CI: 1.01–2.21; p = 0.046). After the subdivision into the groups by age, a significant difference only in the frequency of the MMP-9 (−1562) C/C genotype was found comparing the AMD patients and the control group younger than 65 years (79.7% vs. 66.4%, p = 0.039). Conclusions: Only MMP-9 Rs3918242 (C –> T) single nucleotide polymorphism was found to play a significant role in the development of AMD, and the effect was more pronounced at the age of less than 65 years.

Left ventricular remodelling after acute myocardial infarction: Impact of clinical, echocardiographic parameters and polymorphism of angiotensinogen gene

Introduction: The development of left ventricular remodelling after acute myocardial infarction is a predictor of heart failure and mortality. The purpose of the present study was to assess whether the polymorphism of angiotensinogen (AGT) gene with threonine (T) instead of methionine (M) at amino acid 235 in exon 2 (M235T) had effects on cardiac remodelling after acute myocardial infarction. Methods: One hundred and forty-one patients (mean age 56.4±11.1 years) with a first acute myocardial infarction were enrolled. Within 24–72 hours of the onset of the symptoms and at a four month period two-dimensional echocardiography was performed. Remodelling was defined as a 20% increase from the baseline in left ventricular end-diastolic volume. The genotypes of the study group were compared with the reference group (n=1010) genotypes. AGT M235T polymorphism was determined using polymerase chain reaction amplification. Results: At follow-up, 49 patients (34.7%) were classified as having left ventricular remodelling. Anterior localization of the infarct (p=0.008), leucocyte count at admission (p=0.040), global left ventricular longitudinal strain (p=0.021) and MM genotype of AGT (p=0.024) were independent predictors of ventricular remodelling after myocardial infarction. Conclusions: Anterior wall infarction, increased leucocyte count, decreased longitudinal strain of left ventricular and polymorphism of AGT M235T may predict remodelling after myocardial infarction.

Protective effects of angiotensin-converting enzyme I/I and matrix metalloproteinase-3 6A/6A polymorphisms on dilatative pathology within the ascending thoracic aorta

OBJECTIVE Activation of matrix metalloproteinases and the renin/angiotensin signaling pathways is under investigation with regard to their potential pathogenesis in dilatative pathology of the aorta. The purpose of this study was to explore matrix metalloproteinase-3 5A/6A and angiotensin-converting enzyme I/D polymorphisms as predisposing factors to dilatative pathology of the aorta. METHODS We studied 107 patients who underwent aortic reconstruction surgery due to dilatative pathology of ascending thoracic aorta and a random sample of the population (n = 773), all from Lithuania. The insertion/deletion (-1171 5A/6A) polymorphism in the promoter region of matrix metalloproteinase-3 studied by real-time polymerase-chain-reaction amplification and the D and I alleles were identified on the basis of standard polymerase-chain-reaction amplification of the respective fragments from intron 16 of the angiotensin-converting enzyme gene. RESULTS The frequency of the angiotensin-converting enzyme D allele was significantly higher in dilatative pathology of ascending thoracic aorta patients than in the reference group subjects (0.55 vs 0.48, respectively). The latter group had a significantly higher frequency of the angiotensin-converting enzyme I/I genotype than in dilatative pathology of ascending thoracic aorta patients (27.4% vs 16.5%, respectively). In the reference group, the frequency of combined angiotensin-converting enzyme I/I and matrix metalloproteinase-3 6A/6A genotypes was 7.5%, while in the dilatative pathology of ascending thoracic aorta patient group, there was no one carrying that combined genotype (p = 0.001). CONCLUSIONS The present study showing a role of angiotensin-converting enzyme and matrix metalloproteinase-3 in the development of dilatative pathology of ascending thoracic aorta permits us to entertain a possible protective mechanism for the combined effects of the angiotensin-converting enzyme I/I and the matrix metalloproteinase-3 6A/6A genotypes.

MiRNA profiling of gastrointestinal stromal tumors by next-generation sequencing

Deregulation of miRNAs has been observed virtually in all major types of cancer, whereas the miRNA signature in GIST is not well characterized yet. In this study the first high-throughput miRNA profiling of 15 paired GIST and adjacent normal tissue samples was performed using small RNA-seq approach and differentially expressed miRNAs as well as isomiRNAs were defined. Highly significantly deregulated miRNAs were selected for validation by Taq-Man low-density array in replication group of 40 paired samples. Validated miRNAs were further subjected to enrichment analysis, which revealed significantly enriched KEGG pathways in the main GIST associated pathways. Further, we used an integrated analysis of miRNA-mRNA correlations for KIT and PDGFRA target genes and found a significant correlation between all of the enriched miRNAs and their target gene KIT. Results of the phenotype analysis showed miR-509-3p to be up-regulated in epithelioid and mixed cell types compared to spindle type, whereas miR-215-5p showed negative correlation with risk grade of GIST. These data reveal a detailed miRNA profile of GIST and highlight new candidates that may be important in the development of malignant disease.

Early Age-Related Macular Degeneration in Patients with Myocardial Infarction

Purpose: To investigate the prevalence of early age-related macular degeneration (AMD) in patients with acute myocardial infarction (MI). Methods: Enrolled in the study were 262 acute MI patients (MI group), aged 40–64 years, as well as 1,155 non-MI persons, aged 40–64 years, from a random sample (reference group) of the Kaunas population. Results: The prevalence of early AMD in the random sample was 7.3%, while in MI patients, the prevalence was 54.5% (P < 0.001). For all age groups, the prevalence of early AMD was significantly (P < 0.005) higher in MI patients than in reference-group persons. In the reference group, the prevalence of early AMD increased significantly with age, whereas no such trend was observed in the MI group. At the 45- to 54-year-olds, the prevalence was significantly higher in males than in females (9.9% vs. 3.7%; P < 0.05) in the reference group, while overall, the prevalence of early AMD in the males and females of the much larger reference group was 8.6% versus 6.2%, respectively (P > 0.05). It increased more with age for females (3.7% and 10.8% at the age 45–54 and 55–64 years, P < 0.05, respectively) while in males, frequency of AMD did not differ significantly between latter age groups (9.9% vs. 11.6%; P > 0.05). Conclusions: We conclude that the prevalence of early AMD is significantly higher in patients with MI than in a random sample of the population.

Estimation of the combined effect of Eleutherococcus senticosus extract and cadmium on liver cells.

Cadmium (Cd) is an important industrial pollutant, even though its mechanism of toxicity has not been completely clarified. Cd2+ is toxic to a wide range of organs and tissues. Liver and kidneys are the primary target organs of cadmium toxicity. Cd2+ induces apoptosis and causes necrotic cell death in certain pathophysiological situations. Eleutherococcus senticosus (Rupr. et Maxim.) Maxim. has many beneficial features. It supports the organisms stress response, immune system, and endocrine system, including the adrenal glands, spleen, and thymus gland. The aim of our study was to investigate the effects of the Eleutherococcus senticosus (ES) liquid extract on the accumulation of Cd2+ in liver and on the mitotic and apoptotic activity of liver cells after chronic intoxication by Cd2+. Experiments were carried out on white laboratory mice. Laboratory mice were given to drink solutions of different Cd2+ and ES concentrations for 8 weeks. Cd2+ concentration in mouse liver was detected using atomic absorption spectroscopy. Mitotic and apoptotic activity of liver cells was expressed as an estimated number of mitotic and apoptotic cells in randomly selected reference areas in a histological slide. ES combined with CdCl2 leads to a significant decrease of cadmium concentration in the blood and liver of experimental mice. ES decreased the cadmium‐induced mitotic and apoptotic activity of liver cells.

Effect of clinical factors and gene polymorphism of CYP2C19*2, *17 and CYP4F2*3 on early stent thrombosis

AIM To determine the main clinical and genetic factors having impact on early coronary stent thrombosis. MATERIALS & METHODS Genotyping of CYP2C19*2, *17 and CYP4F2*3 in patients with (n = 31) and without stent thrombosis (n = 456) was performed. Clinical and genetic data were analyzed by binary logistic regression. RESULTS Smoking (OR: 0.317; 95% CI: 0.131-0.767), high-density lipoprotein level in mmol/l (OR: 0.142; 95% CI: 0.040-0.506), CYP2C19*2*2 versus *1*1 and *1*2 genotype (OR: 11.625; 95% CI: 3.498-38.633), CYP4F2 AA versus GA and GG genotype (OR: 3.532; 95% CI: 1.153-10.822) were associated with early stent thrombosis. CONCLUSION For the first time we have identified a clinically important polymorphism (CYP4F2 G1347A) that was independently associated with early stent thrombosis. Original submitted 18 August 2014; Revision submitted 10 November 2014.