Alina Smalinskiene

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.

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.

Influence of Echinacea purpurea (L.) Moench extract on the toxicity of cadmium.

Abstract:  Echinacea purpurea (L.) Moench (EP) has many beneficial features, especially strengthening the immune system. Cadmium (Cd) is a ubiquitous metal and cumulative poison that may cause liver and kidney damage and the formation of neoplasia. In this article, the changes in organs and metabolism, the accumulation of various levels of Cd in tissues, and the effects of EP liquid extract on Cd‐induced changes in mice were investigated. Experiments were carried out on the white laboratory mice. Solution of different Cd and EP concentrations were given to drink and experiments were performed. The concentration of Cd in mice blood, liver, kidneys, heart, spleen, skeletal muscle was determined using an electrothermal graphite furnace atomic absorption spectrophotometer Perkin–Elmer/Zeeman 3030. Long time per os of extract of EP combined with Cd leads to a significant increase of Cd concentration in blood and investigated organs of experiment mice.

Assessment of the Effect of Echinacea purpurea (L.) Moench on Apoptotic and Mitotic Activity of Liver Cells during Intoxication by Cadmium

Abstract:  Cadmium (Cd2+) is an important industrial pollutant, although its mechanism of toxicity has not been completely clarified. Cd2+ is toxic to a wide range of organs and tissues, however, the primary target organs of Cd2+ toxicity are the liver and kidney. Echinacea purpurea stimulating one or another tread of the immune system stimulates the expression of immunoglobulins and interferons. The experiments were performed on white laboratory mice using intraperitoneal (i.p.) injections 0.05 LD50 amount of CdCl2 solution. Two groups of mice were injected by Echinacea purpurea liquid extract: one 0.05 LD50 and the other 0.1 LD50. In this article, the Cd2+ distribution in internal organs, its effect on the mitotic and apoptotic activity of liver cells, as well as effects of Echinacea purpurea liquid extract on Cd2+‐induced changes in mice were investigated. Cd2+ concentration in mice blood, liver, and kidney was detected by atomic absorption spectroscopy. Long‐term injections of extract of Echinacea purpurea combined with Cd2+Cl2 leads to the significant increase of Cd2+ concentration in blood and investigated organs of experimental mice. Mitotic and apoptotic activity of liver cells was expressed as the estimated number of mitotic and apoptotic liver cells in randomly selected reference areas in histological slide. Echinacea purpurea decreases the mitotic activity of liver cells induced by Cd2+ and increases apoptotic activity of the liver cells.

Association between anthropometric indexes and cardiovascular risk factors

The aim of this study was to assess the associations of the body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) with ischemic heart disease (IHD) and risk factors of IHD in the Lithuanian population aged 25 to 70 years. The cross-sectional health survey was carried out in Kaunas, which is the second largest city in Lithuania, and in five regions randomly selected from the northern, southern, eastern, western and central parts of Lithuania. Data from 2048 subjects (936 men and 1112 women) were analyzed. In both sexes, the odds ratios for reduced high density lipoprotein cholesterol, elevated triglycerides, high fasting blood glucose, and hypertension rose with an increasing quartile of BMI, WC, and WHtR. The likelihood of having IHD was statistically significantly higher in the fourth quartile of these anthropometric measures when compared to the first one. Comparison of the logistic regression models revealed that the models with WHtR best fit the prediction of IHD risk. Compared with BMI and WC, WHtR showed a stronger association with IHD and its risk factors in the Lithuanian adult population.

The role of apolipoprotein E (rs7412 and rs429358) in age-related macular degeneration

ABSTRACT Background: Age-related macular degeneration (AMD) is the most common cause of incurable visual impairment in the developed countries. The main pathological change in AMD is the formation of drusen containing 40% of lipids, dominated by esterified cholesterol (EC) and phosphatidylcholine (PC), and protein. Haplotype ε4 of apolipoprotein E (ApoE) acts as a ligand for the low-density lipoprotein receptor and is involved in the maintenance and repair of neuronal cell membranes. Purpose: This study aimed to evaluate the association of AMD with ApoE gene polymorphism variants (rs7412 and rs429358). Methodology: A total of 2133 subjects were enrolled in our research. The study group comprised patients with early AMD (n = 413) and exudative AMD (n = 307), and the control group enrolled randomly selected persons (n = 1413). The genotyping of ApoE (rs7412 and rs429358) was performed using the real-time polymerase chain reaction (PCR) method. Results: Statistical analysis revealed that ApoE 4/2 genotype was less frequently observed in in older patients with exudative AMD compared to older healthy controls (0.4% vs. 4.0%, p = 0.003). Conclusion: Our data demonstrated that ApoE 4/2 genotype was less frequently observed in old patients (65 years and more) with exudative AMD compared to old healthy controls. It leads to hypothesis on the protective effect of ApoE 4/2 to develop AMD in the elderly.

Heritability of myopia and its relation with GDJ2 and RASGRF1 genes in Lithuania

BackgroundThis study aimed to assess heritability of myopia in Lithuania and evaluate both genes GJD2 (Gap Junction Protein, Delta 2) and RASGRF1 (RAS protein-specific guanine nucleotide-releasing factor 1) relation with myopia.MethodsIn this study Lithuanian twin population aged between 18 and 40 (n = 460) were examined. Single-nucleotide polymorphisms of the RASGRF1 (rs8027411) and GJD2 (rs634990) genes were assessed by real-time polymerase chain reaction method.ResultsIntrapair correlations for spherical equivalent in all twin pairs were significantly higher in MZ twin pairs r = 0.539 (p < 0.001, 95% CI 0.353–0.684) than in DZ twin pairs r = 0.203 (p < 0.01, 95% CI 0.0633–0.442) in myopia group. Correlations for spherical equivalent in emmetropia group were not significant in MZ twin pairs r = 0.091 (p > 0.05, 95% CI -0.215-0.381) and in DZ twin pairs r = − 0.220 (p > 0.05, 95% CI -0.587-0.222). The odds ratio (95% CI) were 2.7 (1.018–7.460) for combinations of genotypes of rs634990 CC and rs8027411 GT (p = 0.046).ConclusionsOur studies have shown that the heritability of myopia makes 67.2% in Lithuania. Persons with combinations of genotypes rs634990 CC and rs8027411 GT have 2.7 times higher odds to have myopia.

SCARB1 rs5888 is associated with the risk of age-related macular degeneration susceptibility and an impaired macular area

ABSTRACT Background: Age-related macular degeneration (ARMD), a progressive retinal disease, is responsible for an impaired central vision in about 180 million people worldwide. Current options for ARMD prevention and treatment are limited due to an incomplete understanding of disease etiopathogenesis. We aimed to test the hypothesis that the single nucleotide polymorphism rs5888 of SCARB1 gene reflecting lipid and antioxidant micronutrient metabolism pathways is associated with ARMD susceptibility and to evaluate if there is any relation between SCARB1 rs5888 and the macular lesion area. Materials and methods: The prospective case-control study included patients with ARMD (n = 215) and the reference group (n = 238) drawn from a random sample of the Lithuanian population (n = 1436). The genotyping test of SCARB1 rs5888 was carried out using the real-time polymerase chain reaction method. Results: Regression analysis adjusted by gender and age demonstrated that SCARB1 rs5888 TT genotype significantly decreased the odds for ARMD development (OR: 0.61, 95%; CI: 0.380–0.981, p = 0.04). A smoking habit and leading an outdoor life are associated with larger macular lesion areas in ARMD patients (0.54 (0.00–39.06) vs. 3.09 (0.02–19.30) and 0.27 (0.00–34.57) vs. 0.75 (0.00–39.06), respectively). In late stage ARMD subjects with CT genotype, the macular lesion area was larger than in TT carriers (7.64 (0.49–39.06) mm2 vs. 5.02 (0.03–37.06) mm2, p = 0.006). Conclusions: SCARB1 rs5888 and environmental oxidative stress have a prominent role in ARMD susceptibility, early ARMD progression to advanced stage disease and even in the outcome of the disease—an area of macular lesion.