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Background and Aims: Coronary microvascular dysfunction (CMD) is common after ST-elevation myocardial infarction (STEMI), leading to adverse clinical outcomes. However, its diagnosis remains difficult, and mechanisms elusive. This study explores the role of Trimethylamine N-oxide (TMAO), a gut microbiota metabolite, as a potential biomarker for diagnosing CMD in STEMI patients., Methods: This prospective, observational study enrolled 210 STEMI patients with multivessel coronary artery disease who underwent primary percutaneous coronary intervention (PCI). TMAO levels were measured at baseline, 3 months, and 12 months post-PCI, whilst coronary physiology was assessed at 3 months. The primary endpoint was the incidence of CMD at 3 months, with the secondary endpoint being major adverse cardiovascular and cerebrovascular events (MACCE) at 12 months. An additional 59 consecutive patients were enrolled for validation., Results: TMAO levels varied from baseline to 3 months, then stabilised. The areas under the ROC curve for baseline TMAO and TMAO at 3-month were 0.55 (95 % CI 0.46-0.64; p = 0.426), and 0.80 (95 % CI 0.73-0.87; p < 0.001), respectively. The optimal cut-off for TMAO at 3-month to diagnose CMD was 3.91, with similar sensitivity and specificity in the derivation and validation cohort. The incidence of MACCE was higher in patients with TMAO≥3.91 (41.4 % vs 10.7 %; p < 0.001). The addition of 3-month TMAO improved the diagnostic performance of traditional risk factors., Conclusion: TMAO is a robust biomarker for CMD and is significantly associated with the incidence of MACCE. TMAO has the potential in guiding clinical decision-making and suggests an interplay between gut microbiota and CMD., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Ischemic heart disease (IHD) is the most prevalent type of cardiovascular disease. The main cause of IHD is atherosclerosis, which is a multifactorial inflammatory disease of blood vessels. Studies show that bacteria might have a significant impact on the pathogenesis of atherosclerosis and plaque rupture. This study aimed to evaluate the complexity of interactions between bacteria and the human body concerning metabolites and bacterial genes in patients with ischemic heart disease., Methods: Bacterial 16S rDNA and wcaF , papC , and sdhC genes were detected in whole blood using a real-time PCR methodology. An enzyme-linked immunosorbent assay was used to measure the concentration of the LL-37 protein. An analysis of ARA in blood plasma was performed., Results: Bacterial 16S rDNA was detected in 31% of the study patients, and the genes wcaF and sdhC in 20%. Enterobacterales genes were detected more frequently in patients younger than 65 years than in patients aged 65 years and older ( p = 0.018) and in patients with type 2 diabetes ( p = 0.048). Concentrations of the human antimicrobial peptide LL-37 and 12S-HETE concentrations were determined to be higher if patients had 16S rDNA and biofilm-specific genes., Conclusions: The results of this study enhance the understanding that Enterobacterales bacteria may participate in the pathogenesis of atherosclerosis and IHD. Bacterial DNA and host metabolites in higher concentrations appear to be detected.

Late-life depression (LLD) is a multifactorial disorder, with susceptibility and vulnerability potentially influenced by gene-environment interaction. The aim of this study was to investigate whether the 5-HTTLPR polymorphism is associated with LLD. The sample of 353 participants aged 65 years and over was randomly selected from the list of Kaunas city inhabitants by Residents' Register Service of Lithuania. Depressive symptoms were ascertained using the EURO-D scale. The List of Threatening Events Questionnaire was used to identify stressful life events that happened over the last 6 months and during lifetime. A 5-HTTLPR and lifetime stressful events interaction was indicated by higher odds of depression in those with s/s genotype who experienced high stress compared to l/l carriers with low or medium stress, while 5-HTTLPR and current stressful events interaction analysis revealed that carriers of either one or two copies of the s allele had increased odds of depressive symptoms associated with stress compared to participants with the l/l genotype not exposed to stressful situations. Although no significant direct association was found between the 5-HTTLPR short allele and depression, our findings demonstrated that lifetime or current stressful life events and their modification by 5-HTTLPR genotype are risk factors for late-life depression., (© 2023. Springer Nature Limited.)

Aim: To examine the relationship between patient-provider communication, psychosocial patient self-efficacy, resources and support for self-management and socio-demographics within individualized care of older adults with diabetes., Design: A quantitative study with a cross-sectional survey design., Methods: Data were collected from September 2019 to January 2021 using: Individualized Care Scale, The Communication Assessment Tool, The Diabetes Empowerment Scale and The Resources and Support for Self-Management Scale. Patients with either Type 1 or Type 2 diabetes mellitus that were 65 years old and over (N = 145) participated in the study., Results: The most positive aspects of patient-provider communication were respect and creating a comfortable environment for the patient. A significant relationship was observed between patients' perceptions and support of individualized care and diabetes-related measures. Effective communication was the main factor associated with support for individualizing care, and together with education level, empowerment and access to resources, explained 23% of the variance., (© 2022 The Authors. Nursing Open published by John Wiley & Sons Ltd.)

Background: The NR3C2 gene encodes the mineralocorticoid receptor, which is present on cardiomyocytes. Prior studies reported an association between the presence of NR3C2 single-nucleotide polymorphisms (SNPs) and an increased cortisol production during a stress response such as acute myocardial infarction (AMI), which may lead to adverse cardiac remodeling. Objective: To study the impact of the NR3C2 rs2070950, rs4635799 and rs5522 gene polymorphisms on left ventricular (LV) remodeling, rhythm and conduction disorders in AMI patients. Methods: A cohort of 301 AMI patients who underwent revascularization was included. SNPs of the NR3C2 gene (rs2070950, rs4635799 and rs5522) were evaluated. A total of 127 AMI patients underwent transthoracic echocardiography follow-up after 72 h and 6 months. Results: The rs2070950 GG genotype and rs4635799 TT genotype were most common in patients who had LV end-diastolic volume increase < 20% and the same or increased LV ejection fraction, indicating a possible protective effect of these SNPs. The rs5522 TT genotype was associated with a higher frequency of arrhythmias, while the presence of at least one rs5522 C allele was associated with a lower risk of arrhythmias. Conclusion: SNPs of the NR3C2 gene appear to correlate with better ventricular remodeling and a reduced rate of arrhythmias post-AMI, possibly by limiting the deleterious effects of cortisol on cardiomyocytes.

Background: Antiplatelet drugs, such as ticagrelor, which target platelet P2Y 12 receptors, are used for prevention of ischemic heart disease. Ticagrelor is also known to have pleiotropic effects of unknown mechanisms. Ticagrelor could influence the expression of molecules involved in resolution of inflammation. This study aimed to investigate if ticagrelor could change the expression of CYP4F2 and its encoded protein concentration and, additionally, to determine ticagrelor possible antibacterial activity against gram-negative bacteria., Methods: CYP4F2 expression was determined in HUVEC and HepG2 cell lines by qPCR. CYP4F2 protein concentration was determined by ELISA. Antibiotic susceptibility testing was performed using a disc diffusion method., Results: Ticagrelor was observed to reduce the expression of CYP4F2 in HUVEC and HepG2 cell lines. It also reduced CYP4F2 protein levels in HUVEC cells. Ticagrelor had no bactericidal activity against gram-negative third generation cephalosporin resistant E. coli ., Conclusion: Ticagrelor reduced CYP4F2 protein concentration in HUVEC, and CYP4F2 expression in HUVEC and HepG2 cells, but had no effect on third-generation cephalosporin-resistant E. coli strains., Competing Interests: The authors declare no conflict of interest., (© 2022 Meskauskaite et al.)

Here, we report the emergence of the variant lineage B.1.1.523 that contains a set of mutations including 156&#95;158del, E484K and S494P in the spike protein. E484K and S494P are known to significantly reduce SARS-CoV-2 neutralization by convalescent and vaccinated sera and are considered as mutations of concern. Lineage B.1.1.523 presumably originated in the Russian Federation and spread across European countries with the peak of transmission in April-May 2021. The B.1.1.523 lineage has now been reported from 31 countries. In this article, we analyze the possible origin of this mutation subset and its immune response using in silico methods.

SARS-CoV-2 has spread vastly throughout the word. In this study, we focus on the patterns of spread in Lithuania. By analysing the genetically sequenced data of different lineages and their first appearances, we were able to compare the dynamics of spreading of the lineages and recognize the main possible cause. The impact of emigration patterns and international travel on the variety of lineages was also assessed. Results showed different patterns of spread, and while a vast variety of different lineages were brought in by international travel, many of the viral outbreaks were caused by local lineages. It can be concluded that international travel had the most impact on the spread of SARS-CoV-2.

As there is some evidence that the risk for Alzheimer's disease (AD) is partially attributable to environmental exposure to some metals and metalloids, we examined an association between AD and arsenic, chromium, and selenium in 53 AD patients and 217 controls. Urinary arsenic, blood chromium, and selenium were determined by inductively coupled plasma mass spectrometry. Logistic regression models calculating odds ratios (ORs) and 95% confidence intervals (CI) were used to estimate AD association with arsenic, chromium, and selenium. In AD patients, urinary arsenic and blood chromium were significantly higher, while blood selenium was significantly lower compared to controls. Increased blood selenium was related to a significant decrease in the odds of AD after adjustment for risk factors. Blood selenium per 1 kg × 10 -9 /m 3 × 10 -4 increment was associated with 1.4 times lower risk of AD (OR = 0.71; 95% CI 0.58-0.87). A significant increase in the odds of AD associated with increased blood chromium was also seen in the adjusted model: the OR per 1 kg × 10 -9 /m 3 × 10 -3 chromium increment was 2.39 (95% CI 1.32-4.31). The association of urinary arsenic with the risk of AD was not significant. The data obtained provide evidence that selenium reduces the risk of Alzheimer's disease, while chromium increases it.

Aims: The goals of this study were to develop a new technique that could pave the way for a quicker determination of CYP4F2 rs3093135 and CYP2C19 rs4244285 variants directly from a patient's blood and to attempt to apply this technique in clinical practice. Patients & methods: The study included 144 consecutive patients admitted with ST elevation myocardial infarction. A blood-direct PCR and real-time PCR were used to detect variants of interest. Results & conclusion: Patients with bleeding events had the CYP2C19 GG (*1*1) variant more frequently than patients without bleeding events. The CYP4F2 TT variant was more frequently detected in patients with bleeding events 3 months after hospitalization.

Background: Evidence shows that microRNAs (miRNAs) could play a key role in the homeostasis and development of major depressive disorder and bipolar disorder. The present study is aimed at investigating the changes in circulating miRNA expression profiles in a plasma of patients suffering from major depressive disorder (MDD) and bipolar disorder (BD) to distinguish and evaluate these molecules as biomarkers for mood disorders., Methods: A study enrolled a total of 184 subjects: 74 controls, 84 MDD patients, and 26 BD patients. Small RNA sequencing revealed 11 deregulated circulating miRNAs in MDD and BD plasma, of which expression of 5, hsa-miR-139-3p, miRNAs hsa-let-7e-5p, hsa-let-7f-5p, hsa-miR-125a-5p, and hsa-miR-483-5p, were further verified using qPCR. miRNA gene expression data was evaluated alongside the data from clinical assessment questionnaires., Results: hsa-let-7e-5p and hsa-miR-125a-5p were both confirmed upregulated: 0.75-fold and 0.25-fold, respectively, in the MDD group as well as 1.36-fold and 0.68-fold in the BD group. Receiver operating curve (ROC) analysis showed mediocre diagnostic sensitivity and specificity of both hsa-let-7e-5p and hsa-miR-125a-5p with approximate area under the curve (AOC) of 0.66. ROC analysis of combined miRNA and clinical assessment data showed that hsa-let-7e-5p and hsa-miR-125a-5p testing could improve MDD and BD diagnostic accuracy by approximately 10%., Conclusions: Circulating hsa-let-7e-5 and hsa-miR-125a-5p could serve as additional peripheral biomarkers for mood disorders; however, suicidal ideation remains the major diagnostic factor for MDD and BD., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Dovydas Gecys et al.)

Background: Individualized nursing care as a form of person-centered care delivery is a well-known approach in the health care context and is accepted as best practice by organizations and professionals, yet its implementation in everyday practice creates serious challenges. The aim was to assess and compare the perceptions of health professionals and older diabetes patients on their individual care in regard to the patient's clinical situation, personal life situation, and decisional control., Methods: The quantitative study with a cross-sectional survey design was conducted from March 2019 until January 2021. The Individualized Care Scale was applied for the data collection. Health professionals (nurses and physicians, n = 70) and older diabetes patients ( n = 145) participated in the study. The average duration of diabetes was 15.8 years (SD = 10.0) and type 2 diabetes was the most common (89.0%). The current glucose-lowering therapy for 51.0% of the patients was oral medications, 37.9% used injected insulin, and 11.1% were treated by combined therapy., Results: The highest-rated aspects of individualized care on both dimensions of the scale from the health professionals' perspective related to the clinical situation, and the scores for provision were significantly higher than those for support. The highest means of patients' ratings on the support dimension related to the clinical situation and the decisions over care sub-scale; for the care provision dimension, the highest individuality in care was assigned to the decisions over care sub-scale. The lowest ratings of individualized care, both in the health professionals' and patients' samples, related to the personal life situation sub-scale., Conclusions: Health professionals are more positive in regard to individualized care support and provisions for older diabetes patients than the patients themselves. Patient characteristics, such as the type of glucose-lowering therapy, education, and nutritional status, make a difference in patients' understanding and experience of individuality in care.

MC4R , LEP , and LEPR genes are involved in the hypothalamic leptin-melanocortin regulation pathway, which is important for energy homeostasis. Our study aimed to evaluate the associations between the MC4R rs17782313, LEP rs7799039, and LEPR rs1137101 polymorphisms with obesity-related parameters in childhood and adulthood. The data were obtained from the Kaunas Cardiovascular Risk Cohort study, which started in 1977 with 1082 participants aged 12-13 years. In 2012-2014, the follow-up survey was carried out. Genotype analysis of all respondents ( n = 509) aged 48-49 years was performed for the gene polymorphisms using Real-Time Polymerase Chain Reaction. Anthropometric measurements were performed in childhood and adulthood. In childhood, only skinfold thicknesses were associated with gene variants being the lowest in children with MC4R TT genotype and LEP AG genotype. In adulthood, odds of obesity and metabolic syndrome was higher in MC4R CT/CC genotype than TT genotype carriers (OR 1.8; 95% CI 1.2-2.8 and OR 1.6; 95% CI 1.1-2.4, respectively). In men, physical activity attenuated the effect of the MC4R rs17782313 on obesity. The LEP GG genotype was associated with higher BMI, waist circumference, and visceral fat level only in men. No associations of the LEPR rs1137101 polymorphisms with anthropometric measurements and leptin level were found. In conclusion, the associations of the MC4R and LEP gene polymorphisms with obesity-related parameters strengthened with age.

Background and Objectives : Serum cortisol has been extensively studied for its role during acute myocardial infarction (AMI). Reports have been inconsistent, with high and low serum cortisol associated with various clinical outcomes. Several publications claim to have developed methods to evaluate cortisol activity by using elements of complete blood count with its differential. This study aims to compare the prognostic value of the cortisol index of Endobiogeny with serum cortisol in AMI patients, and to identify if the risk of mortality in AMI patients can be more precisely assessed by using both troponin I and cortisol index than troponin I alone. Materials and methods : This prospective study included 123 consecutive patients diagnosed with AMI. Diagnostic coronary angiography and revascularization was performed for all patients. Cortisol index was measured on admission, on discharge, and after 6 months. Two year follow-up for all patients was obtained. Results : Our study shows cortisol index peaks at 7-12 h after the onset of AMI, while serum cortisol peaked within 3 h from the onset of AMI. The cortisol index is elevated at admission, then significantly decreases at discharge; furthermore, the decline to its bottom most at 6 months is observed with mean values being constantly elevated. The cortisol index on admission correlated with 24-month mortality. We established combined cut-off values of cortisol index on admission > 100 and troponin I > 1.56 μg/las a prognosticator of poor outcomes for the 24-month period. Conclusions : The cortisol index derived from the global living systems theory of Endobiogeny is more predictive of mortality than serum cortisol. Moreover, a combined assessment of cortisol index and Troponin I during AMI offers more accurate risk stratification of mortality risk than troponin alone.

Objective: To determine the association of genetic variants rs7901695, rs7903146, rs7895340, rs11196205, rs12255372 of transcription factor 7 like 2 (TCF7L2) gene and its coherence with metabolic parameters in Lithuanian (Kaunas district) women population with previously diagnosed gestational diabetes mellitus (GDM) and to compare the prevalence of TCF7L2 single nucleotide polymorphism (SNP) results to general population., Methods: Women with previously diagnosed GDM participated in the study. Anthropometric measurements were taken. Carbohydrate and fat metabolism were evaluated. TCF7L2 SNP common variants (rs7901695, rs7903146, rs7895340, rs11196205, rs12255372) were set. The prevalence of TCF7L2 the same SNP alleles were also evaluated for women of the general population. The results were compared to the main study group (women with previously diagnosed GDM). The results were calculated in a ratio of 1:2. General population group comprised 300 women who were selected from the random sample of the Kaunas city population. Statistical analysis was made with the statistical package IBM SPSS Statistics version 21. Quantitative parametric variables presented as mean and standard deviation, qualitative variables - as absolute numbers and percentage. ANOVA test was used, for the comparison between three or more groups. Quantitative variables were compared using Student's t-test. Categorical variables were compared using chi-square test. Correlation analysis of parametrical data was performed by Pearson's correlation. Odds ratios (OR) with 95% CIs were presented. The results were considered statistically significant at p < 0.05., Results: 158 women with previously (15-47 years ago) diagnosed GDM participated in the study. The mean age of participants was 53.0 ± 8.2 years and 60.2 ± 7.5 years (p < 0.001), BMI - 31.4 ± 7.9 kg/m 2 and 29.9 ± 5.8 kg/m 2 (p < 0.001) in GDM group and general population respectively. GDM group women had significantly larger waist, hip circumference and waist to hip ratio compared to general population women: 98.9 ± 18.1 cm vs. 89.2 ± 13.3 (p < 0.001), 112.5 ± 14.8 cm vs. 105.6 ± 10.9 cm (p < 0.001), 0.87 ± 0.08 vs. 0.84 ± 0.07 (p < 0.001). There was no significant difference in blood pressure results between groups (p > 0.05). Carbohydrate dysmetabolism was set for 57.6% women with previously diagnosed GDM: 11 (7.0%) were diagnosed with impaired fasting glycemia (IFG), 14 (8.9%) with impaired glucose tolerance (IGT), type 2 Diabetes Mellitus (DM) was diagnosed for 58 (36.7%), DM type 1 for 7 (4.4%), MODY2 (maturity onset diabetes of the young) - 1 (0.6%) patients. TCF7L2 SNPs in women with previously diagnosed GDM and various carbohydrate metabolism groups did not differed (p > 0.05). Body weight, body mass index (BMI), waist and hip circumference in GDM group participants with different TCF7L2 SNP alleles did not differ (p > 0.05). There was no statistically significant difference in fasting plasma glucose (FPG), oral glucose tolerance test (OGTT) results, cholesterol levels and different TCF7L2 SNP alleles in GDM group (p > 0.05). We found higher prevalence of TCF7L2 SNP rs7901695 CC/CT, rs7903146 CT/TT and rs12255372 GT/TT alleles in women previously diagnosed GDM compared to general population women's group. The OR of being in GDM group with TCF7L2 SNP: rs7901695 CC/CT alleles, was 1.703 (95% CI 1.153-2.515); rs7903146 CT/TT - 1.708 (95% CI 1.149-2.538); rs12255372 GT/TT - 1.575 (95% CI 1.058-2.343)., Conclusions: No statistically significant difference in glucose, cholesterol levels and different TCF7L2 SNP alleles in GDM group was found. TCF7L2 SNPs did not differed in women with previously diagnosed GDM and various carbohydrate metabolism groups, though a significantly higher incidence of TCF7L2 rs7901695 SNP CC/CT, rs7903146 SNP CT/TT, rs12255372 GT/TT alleles in study subjects compared to the general population women were observed., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Antiplatelet drugs are prescribed without considering the diabetic status of the patient. The objective of the current investigation was to determine the impact of clinical factors, CYP4F2 enzyme and 20-hydroxyeicosatetraenoic acid (20-HETE) concentrations on high on-treatment platelet reactivity in patients with diabetes treated with antiplatelet drugs following acute coronary syndromes. A total of 667 patients were included in the study. Dual antiplatelet drug loading dosages with aspirin (300 mg) and ticagrelor (180 mg) or clopidogrel (600 mg) were prescribed to all the studied patients. Testing of platelet aggregation was performed the day after loading antiplatelet drug dosages. Platelet aggregation test was done according to the classical Born method. Multivariate binary regression analysis demonstrated that insulin use and higher 20-HETE concentration increased the odds of high on-treatment platelet reactivity during the initiation of antiplatelet drug therapy (OR: 3.968, 95% CI: 1.478-10.656, p = 0.006 and OR: 1.139, 95% CI: 1.073-1.210, respectively, p < 0.001). Ticagrelor use decreased the odds of developing high on-treatment platelet reactivity (OR: 0.238, 95% CI: 0.097-0.585, p = 0.002). Data from this study revealed that high on-treatment platelet reactivity during dual antiplatelet therapy in patients with diabetes may depend on such factors as insulin prescription and 20-HETE concentration.

Purpose: To find an association of relative expression of hsa-miR-24-3p and hsa-miR-34a-5p molecules and CYP4F2 enzyme activity in blood plasma of stable angina pectoris (AP) patients'. Materials and Methods: MiRNA gene expression analysis was performed on total RNA extracted from blood plasma, using quantitative real-time polymerase chain reaction. CYP4F2 enzyme levels were determined using commercial ELISA kit. In total, 32 AP and 15 control samples were examined. Results: The relative expression of hsa-miR-24-3p and hsa-miR-34a-5p was upregulated by 4.4 ( p  = 0.0001) and 3.8 ( p  = 0.005) -fold in AP patient's blood plasma compared to control subjects. CYP4F2 enzyme level in blood plasma were 2.1 ( p  = 0.001) times lower in AP patients. Circulating hsa-miR-24-3p was negatively associated with CYP4F2 enzyme level (Spearman correlation coefficient rank r = -0.32; p  = 0.03). Moreover, patients that were taking atorvastatin, had 1.5 ( p  = 0.04) times higher hsa-miR-24-3p expression in blood plasma. Conclusions. Our data suggest that hsa-miR-24-3p might have an effect on CYP4F2 activity during atherosclerosis.

Background/aim: The matrix metalloproteinases (MMP) play an important role in the physiological and pathological remodeling of tissues including carcinogenesis. The study's aim was to assess the relations between MMP-2(-735C/T), MMP-2(-1306C/T), MMP-9(-1562C/T), and MMP-3(-11715A/6A) polymorphisms, and clinical/morphological manifestation of laryngeal squamous cell carcinoma (LSCC) and benign vocal fold lesions (BVFL)., Patients and Methods: Two hundred and seventeen patients with LSCC and BVFL and 458 controls were included in this study. The genotyping was performed using the real-time polymerase chain reaction method., Results: The MMP-2(-1306C/T) C/T genotype was significantly rarer among the patients with moderate-poorly differentiated LSCC compared to the control group, however the MMP-3(-11715A/6A) 6A/6A genotype was significantly more frequent compared to controls. Smoking and 6A/6A genotype of MMP-3(-11715A/6A) polymorphism were associated with increased odds of LSCC risk. No associations between MMP genotypes and BVFL were found., Conclusion: Smoking and MMP-3 (-11715A/6A) 6A/6A genotype may cause a higher risk for developing LSCC., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

The cytochrome P450 (CYP)4F2 gene is known to influence mean coumarin dose. The aim of the present study was to undertake a meta-analysis at the individual patients level to capture the possible effect of ethnicity, gene-gene interaction, or other drugs on the association and to verify if inclusion of CYP4F2*3 variant into dosing algorithms improves the prediction of mean coumarin dose. We asked the authors of our previous meta-analysis (30 articles) and of 38 new articles retrieved by a systematic review to send us individual patients' data. The final collection consists of 15,754 patients split into a derivation and validation cohort. The CYP4F2*3 polymorphism was consistently associated with an increase in mean coumarin dose (+9% (95% confidence interval (CI) 7-10%), with a higher effect in women, in patients taking acenocoumarol, and in white patients. The inclusion of the CYP4F2*3 in dosing algorithms slightly improved the prediction of stable coumarin dose. New pharmacogenetic equations potentially useful for clinical practice were derived., (© 2018 The Authors Clinical Pharmacology & Therapeutics © 2018 American Society for Clinical Pharmacology and Therapeutics.)

The aim of this study was to evaluate the association of ADM genetic variant and HBP among Lithuanian adolescents aged 12-15 years. This is a cross-sectional study of a randomly selected sample of 675 12-15-years-old schoolchildren who were surveyed during November 2010 to April 2012 in the baseline survey. Single-nucleotide polymorphism (SNP) of ADM gene (rs7129220) was evaluated using real-time PCR. Logistic regression analyses were used to test the associations of ADM (rs7129220) polymorphism with HBP under four inheritance models based on the Akaike Information Criterion (AIC) and to calculate the odds ratios. In the multivariate analysis, boys carrying ADM AG genotype (vs. carriers of ADM GG genotype), ADM AG + AA genotype (vs. carriers of ADM GG genotype) and ADM AG genotype (vs. carriers of ADM GG + AA genotype) had higher odds of having hypertension in codominant, dominant, and overdominant inheritance models. Girls with ADM AG + AA had increased odds of prehypertension compared to girls with the ADM GG genotype carriers in dominant inheritance model. Significant associations were observed in additive models separately for boys (hypertension) and girls (prehypertension). Our results indicate that ADM gene polymorphism was significantly associated with higher odds of HBP in Lithuanian adolescents aged 12-15 years.

Aim: The aim of this study was to determine the impact of genetic and nongenetic factors on treatment outcomes in patients receiving dual antiplatelet therapy after percutaneous coronary intervention and stent implantation. Materials & methods: Patients (n = 628) used clopidogrel or ticagrelor for at least 1 week before platelet aggregation test. Results: Multivariate binary regression analysis demonstrated that aspirin use and CYP4F2 T allele significantly increased odds for bleeding in clopidogrel users (OR: 2.488, 95% CI: 1.452-4.265; p = 0.001 and OR: 1.573, 95% CI: 1.066-2.320; respectively; p = 0.022). CYP4F2 T allele significantly increased odds for bleeding in ticagrelor users (OR: 8.270, 95% CI: 3.917-17.462; p < 0.001). Conclusion: Aspirin use and CYP4F2 T allele were significantly associated with bleeding during dual antiplatelet therapy.

Purpose: For long time, blood clot retraction was measured only by thromboelastographic or platelet contractile force measurement techniques. The purpose of the present study was development of a novel ultrasonic method based on simultaneous monitoring of variations in the ultrasound velocity and the frequency spectrum of the signal propagating in clotting blood and its application for automatic evaluation of blood clotting parameters., Methods: Simultaneous measurement of ultrasound velocity and variations in the frequency spectrum of wideband ultrasonic signals in clotting blood samples was performed. All measurements were performed in pulse-echo mode. Standard clinical data were obtained using routine clinical laboratory methods., Results: The amplitudes of ultrasonic signals during native blood coagulation varied up to ten times for different frequencies. The measurement results of the start and duration of blood clot retraction differed between patient samples: different components of the blood coagulation system had significant impact on the blood clot retraction process., Conclusions: Our results showed that during blood clotting, the ultrasound velocity and variations in frequency spectrum should be used simultaneously to determine the beginning and duration of blood clot retraction. Our results also showed that blood clot retraction is controlled by the activity of factor XIII.

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.

Objectives: Recently, genome-wide associated studies have identified several genetic loci that are associated with elevated blood pressure and could play a critical role in intracellular calcium homeostasis. The aim of this study was to assess the associations of ATP2B1 rs2681472 and CACNB2 rs12258967 gene polymorphisms with high blood pressure (HBP) among Lithuanian children and adolescents aged 12-15 years., Study Design and Participants: This was a cross-sectional study of a randomly selected sample of 646 12-15-year-old adolescents who participated in the survey 'The Prevalence and Risk Factors of HBP in 12-15 Year-Old Lithuanian Children and Adolescents (from November 2010 to April 2012)'. Anthropometric parameters and BP were measured. The participants with HBP were screened on two separate occasions. Subjects were genotyped ATP2B1 rs2681472 and CACNB2 rs12258967 gene polymorphisms using real-time PCR method., Results: The prevalence of HBP was 36.7%, significantly higher for boys than for girls. In the multivariate analysis, after adjustment for body mass index and waist circumference, boys with CACNB2 CG genotype, CACNB2 GG genotype and CACNB2 CG +GG genotype had higher odds of having HBP in codominant (adjusted OR (aOR)=1.92; 95% CI 1.16 to 3.18, p=0.011; and aOR=2.64; 95% CI 1.19 to 5.90, p=0.018) and in dominant (aOR=2.05; 95% CI 1.27 to 3.30, p=0.003) inheritance models. Girls carrying CACNB2 CG genotype and CACNB2 CG +GG genotype had increased odds of HBP in codominant (aOR=1.82; 95% CI 1.02 to 3.24, p=0.044) and in dominant (aOR=1.89; 95% CI 1.09 to 3.28, p=0.023) inheritance models. Furthermore, significant associations were found in additive models separately for boys (aOR=1.72; 95% CI 1.20 to 2.46, p=0.003) and girls (aOR=1.52; 95% CI 1.05 to 2.20, p=0.027). No significant association was found between ATP2B1 gene polymorphism and the odds of HBP., Conclusions: Our results indicate that CACNB2 gene polymorphism was significantly associated with higher odds of HBP in Lithuanian adolescents aged 12-15 years., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Dilatative pathology of the ascending thoracic aorta (DPATA) is characterized by the aortic wall expansion more than 1.5 and could be accompanied by aortic wall rupture. Mutations of TGFBR2 gene demonstrated an association with syndromic DPATA and altered pathway of transforming growth factor beta (TGF-β). Elevated TGF-β1 level has been found in blood samples in DPATA group. Moreover, elevated osteopontin (OPN) level was associated with mutations of TGFBR2 gene. Based on recently published findings, we aimed to evaluate genotyping results of TGFBR2 rs4522809 and the association with circulating OPN and TGF-β1 concentrations within DPATA patients., Methods and Findings: TGFBR2 SNP genotyping assay was performed by quantitative real-time PCR, TGF-β1 and OPN concentrations were measured using enzyme-linked immunosorbent assay. Genotyping results showed G allele to be associated with DPATA (p = .01), the presence of G allele significantly increased the possibility of DPATA by 1.67 times (OR = 1.67, 95%, CI = 1.12-2.47). TGF-β1 concentration was significantly higher in DPATA subjects compared with Reference group (p = 0,001). Finally, we found moderate inverse correlation (r = -0,524) between circulating TGF-β1 and OPN levels within DPATA subjects (p = 0,002), as increasing levels of TGF-β1 cytokine significantly decrease concentration of OPN., Conclusions: This is the first report on the association between previously defined TGFβR2 SNP rs4522809 linked with dilatation of ascending thoracic aorta. Also, for the first time we report the inversed correlation between circulating TGF-β1 and OPN concentrations in DPATA subjects indicating the possible biomarkers for DPATA., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

: The aim of the current study was to evaluate the impact of CYP2C192 (rs4244285), CYP4F23 (rs2108622), and nongenetic factors on platelet aggregation and to investigate the mechanism of CYP4F2's effect on platelet aggregation in the patients treated with dual antiplatelet therapy. A total of 146 patients were included in this study. Ticagrelor or clopidogrel were administered in a loading dose of 180 mg and 600 mg, respectively, in combination with aspirin (300 mg). Blood samples for analysis were taken the next morning after antiplatelet therapy induction. Clopidogrel users with the CYP2C1912 variant had higher platelet aggregation values (median 43, range 30-54%) compared with 11 wild-type carriers (median 33, range 15-77%; P = 0.009). Carriers of the CYP4F213 variant had higher platelet aggregation values than carriers of the 33 variant (median 34, range 8-70% vs. median 24.5, range 10-47%, P = 0.016, respectively). Higher CYP4F2 concentrations were detected in clopidogrel users than in ticagrelor users (median 3.6, range 1.6-22.0 ng/ml vs. median 2.3, range 1.6-27.2 ng/ml, P = 0.056, respectively) and in carriers of the CYP4F213 variant compared with carriers of the 11 variant (median 4.3, range 1.6-27.2 ng/ml vs. median 2.4, range 1.6-22.0 ng/ml, P = 0.009, respectively). No correlation between plasma 20-hydroxyeicosatetraenoic acid and CYP4F2 enzyme concentrations were detected (r = -0.045, P = 0.587). Our results proved that CYP2C192 might significantly affect antiplatelet function of clopidogrel. Plasma CYP4F2 concentrations were significantly lower in ticagrelor users than in clopidogrel users.

Objective: A case-control study was conducted to assess seasonal influenza vaccine effectiveness (SIVE) during the 2015-2016 influenza season., Methods: A study was performed in three departments in Lithuania between 1 December 2015 and 1 May 2016. Data on demographic and clinical characteristics including influenza vaccination status were collected from the patients recommended to receive the seasonal influenza vaccine. Influenza virus infection was confirmed by multiplex reverse transcription polymerase chain reaction (RT-PCR) ., Results: Ninety-one (56.4%) of the 163 included subjects were ≥65 years old. Fifteen (9.2%) subjects were vaccinated against influenza at least 2 weeks before the onset of influenza symptoms, 12 of them were ≥65 years old. Of the 72 (44.2%) influenza virus positive cases, 65 (39.9%) were confirmed with influenza A (including 50 cases of influenza A(H1N1)pdm09), eight (4.9%) were confirmed with influenza B and one was a co-infection. Unadjusted SIVE against any influenza, influenza type A and influenza A(H1N1)pdm09 was 57% (95% CI -41% to 87%), 52% (95% CI -57% to 85%) and 70% (95% CI -43% to 94%) respectively., Conclusion: Although SIVE estimates were not statistically significant the point estimates suggest moderate effectiveness against influenza type A., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Aim: To examine the MMP-2 (-1306 C/T) gene polymorphism and the phenotype characterized by soft and hard drusen of early age-related macular degeneration (AMD) and geographic atrophy of late AMD form., Methods: The study enrolled 850 investigations (290 AMD patients with soft and hard drusen, 34 with geographic atrophy and a random sample of the population n =526). Early AMD was classified according to the International Classification and Grading System. For geographic atrophy diagnosis the Age-Related Eye Disease Study classification was used. The potential association with single nucleotide polymorphisms on MMP-2 Rs243865 was evaluated for all patients, adjusted for age and sex. The genotyping test of MMP-2 Rs243865 (C-->T) was conducted using the real-time polymerase chain reaction method., Results: MMP-2 (-1306 C/T) C/C genotype was more frequently detected in AMD patients with hard drusen than the soft drusen or control group (66.43% vs 53.74%, vs 54.94%, P =0.047). Logistic regression analysis showed that the MMP-2 (-1306) C/C genotype increased the likelihood to develop hard drusen in AMD patients (OR=1.7, 95% CI: 1.06-2.74; P =0.028). No association between MMP-2 (-1306 C/T) gene polymorphism in patients with atrophic AMD and control group was found (54.94%, 37.64%, 7.41% vs 50%, 38.24%, 11.76%; P =0.6)., Conclusion: The MMP-2 Rs24386 (C-->T) polymorphism is found to be associated with the development of hard drusen in patients with AMD.

Background: Epidemiological studies have demonstrated the influence of environmental factors on HBP in the population of Lithuanian children, although the role of genetic factors in hypertension has not yet been studied. The aim of this study was to assess the distribution of AGTR1, AGT, and ACE genotypes in the Lithuanian child population and to determine whether these genotypes have an impact on HBP in childhood., Methods: This cross-sectional study enrolled 709 participants aged 12-15 years. The subjects were genotyped for AGT (M235 T, rs699), AGTR1 (A1166C, rs5186), and ACE (rs4340) gene polymorphisms using real-time and conventional polymerase chain reactions. Blood pressure and anthropometric parameters were measured., Results: The prevalence of HBP was 38.6% and was more frequently detected in boys than in girls (47.9% vs. 29.5%; p < 0.001). No significant differences in the frequencies of the AGT or AGTR1 genotypes or alleles between boys and girls were observed, except for ACE genotypes. The mean SBP value was higher in HBP subjects with ACE ID genotype compared to those with ACE II homozygotes (p = 0.04). No significant differences in BP between different AGT and AGTR1 genotype groups were found. Boys who carried the ACE ID + DD genotypes had higher odds of having HBP than carriers of the ACE II genotype did (controlling for the body mass index (BMI): OR MH  = 1.83; 95% CI, 1.11-3.02, p = 0.024; and controlling for waist circumference (WC): OR MH  = 1.76; 95% CI, 1.07-2.92, p = 0.035). These associations were not significant among girls. The same trend was observed in the multivariate analysis - after adjustment for BMI and WC, only boys with ACE ID genotype and ACE ID + DD genotypes had statistically significantly increased odds of HBP (aOR = 2.05; 95% CI, 1.19-3.53 (p = 0.01) and aOR = 1.82; 95% CI, 1.09-3.04 (p = 0.022), respectively)., Conclusions: The evaluated polymorphisms of the AGT and AGTR1 genes did not contribute to the presence of HBP in the present study and may be seen as predisposing factors, while ACE ID genotypes were associated with significantly increased odds for the development of HBP in the Lithuanian child and adolescent population - especially in boys.

Aim: To determine clinically significant factors which may alter the effect of dual antiplatelet therapy with aspirin and ticagrelor or clopidogrel in patients who had undergone percutaneous coronary intervention and stent implantation., Materials & Methods: The study included 378 patients. All the patients had undergone percutaneous coronary intervention and stent implantation. Platelet aggregation and genotyping for CYP2C19 *2 (rs4244285) and CYP4F2 (rs2108622, rs1558139, rs3093135 and rs2074902) was performed., Results: Significantly lower platelet aggregation values (% agr ) were detected in ticagrelor users who carried CYP4F2 rs3093135 TT variant (14.67 ± 5.07% agr ) versus AA (22.88 ± 6.30% agr ), p = 0.0004, or AT (20.56 ± 6.51% agr ), p = 0.0126., Conclusion: Results of the current study showed that CYP4F2 rs3093135 TT variant carriers had a higher antiplatelet effect of ticagrelor, and more frequently had nonprocedural bleeding during ticagrelor therapy, as compared with AA and AT variant carriers.

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.

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) mm 2 vs. 5.02 (0.03-37.06) mm 2 , 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.

Cardiovascular diseases are the most common cause of mortality and morbidity in most populations. As the traditional modifiable risk factors (smoking, hypertension, dyslipidemia, diabetes mellitus, and obesity) were defined decades ago, we decided to analyze recent data in patients who survived acute coronary syndrome (ACS). The Czech part of the study included data from 999 males, and compared them with the post-MONICA study (1,259 males, representing general population). The Lithuanian study included 479 male patients and 456 age-matched controls. The Kazakhstan part included 232 patients and 413 controls. In two countries, the most robust ACS risk factor was smoking (OR 3.85 in the Czech study and 5.76 in the Lithuanian study), followed by diabetes (OR 2.26 and 2.07) and hypertension (moderate risk elevation with OR 1.43 and 1.49). These factors did not influence the ACS risk in Kazakhstan. BMI had no significant effect on ACS and plasma cholesterol was surprisingly significantly lower (P<0.001) in patients than in controls in all countries (4.80+/-1.11 vs. 5.76+/-1.06 mmol/l in Czechs; 5.32+/-1.32 vs. 5.71+/-1.08 mmol/l in Lithuanians; 4.88+/-1.05 vs. 5.38+/-1.13 mmol/l in Kazakhs/Russians). Results from our study indicate substantial heterogeneity regarding major CVD risk factors in different populations with the exception of plasma total cholesterol which was inversely associated with ACS risk in all involved groups. These data reflect ethnical and geographical differences as well as changing pattern of cardiovascular risk profiles.

Background: Two-dimensional (2D) echocardiography is one of the most feasible, noninvasive methods for assessing the aortic diameter and biomechanical changes. We studied possible interfaces between noninvasive biomechanical and speckle-tracking (ST) echocardiographic data from dilated aortas., Methods: Altogether, 44 patients with dilative pathology of ascending aorta (DPAA) were compared with subjects without ascending aortic dilation (diameter <40 mm). DPAA patients formed two groups based on diameter size: group 1, ≤45 mm diameter; group 2, >45 mm. Conventional and 2D-ST echocardiography were performed to evaluate peak longitudinal strain (LS), longitudinal (LD) and transverse (TD) displacement, and longitudinal velocity (VL). Aortic strain, distensibility, elastic modulus, stiffness index β of Valsalva sinuses and ascending aorta were also evaluated. SPSS version 20 was used for all analyses., Results: All linear diameters of the ascending aorta were increased in group 2 (>45 mm diameter) (p < 0.05). LD of the anterior aortic wall (p < 0.05) and TD of both aortic walls (p < 0.001) were least in group 2. VL of the posterior and anterior walls diminished in group 2 (p = 0.01). Aortic strain and distensibility were least (p = 0.028 and p = 0.001, respectively) and elastic modulus and stiffness index β values were greatest in group 2, although without statistical significance., Conclusions: Ascending aortas of both DPAA groups had reduced elasticity and increased stiffness. The greatest changes in biomechanical parameters occurred in ascending aortas >45 mm. Longitudinal ascending aortic wall motion was mostly impaired in patients with aortas >45 mm (i.e., anterior aortic wall LD, VL of the posterior and anterior walls. TD of the posterior and anterior aortic walls was significantly lower in >45 mm aortic diameter patients. TD of 5.2 mm could predict aortic dilation >45 mm (area under the curve 0.76, p < 0.001, confidence interval 0.65-0.87; sensitivity 87%; specificity 63%). Greater aortic dilation is associated with reduced aortic stiffness parameters and increased elastic modulus and stiffness index β. Lower LD and LS were associated with less aortic strain and distensibility. There were no significant differences in 2D-ST echocardiographic or stiffness parameters between patients with tricuspid or bicuspid aortic valves.

We present two clinical cases of acute and subacute coronary artery stent thrombosis in patients treated at the Department of Interventional Cardiology in Aktobe, Kazakhstan. Our results draw attention to the impact of CYP3A4*1B on the clinical effect of clopidogrel during dual antiplatelet therapy after PCI. The genotyping performed at the Laboratory of Molecular Cardiology of Institute of Cardiology of Lithuanian University of Health Sciences in Lithuania revealed that both patients were homozygous carriers of CYP3A4*1B*1B. They also were carriers of CYP2C19 loss-of-function *2 or *3 alleles (*1*2 and *1*3, respectively).

Purpose: To determine if the frequency of the MMP-2 (-1306 C/T) genotype has an influence on the development of early age-related macular degeneration (AMD)., Methodology: The study enrolled 387 patients with early AMD and a random sample of 682 healthy persons (control group). The genotyping of MMP-2 (-1306 C/T) was carried out using the real-time polymerase chain reaction method., Results: The analysis of the MMP-2 (-1306 C/T) gene polymorphism did not reveal any differences in the genotype distribution between the patients with AMD and the control subjects. When the study population was divided into age groups, the C/C genotype was more prevalent in the AMD patients aged <65 years than those aged ≥65 years (65.19% versus 53.88%, p = 0.0294), and the C/T genotype was more frequent in the AMD patients aged ≥65 years when compared with the AMD patients aged <65 years (40.78% versus 26.52%, p = 0.0037). Moreover, in the female group younger than 65 years, the frequency of the C/C genotype was greater in the AMD group than the control group (75% versus 58.91%, p = 0.0232)., Conclusions: This study showed a significantly greater prevalence of the C/C and C/T genotypes in the patients with AMD younger than 65 years and those aged ≥65 years, respectively. Moreover, the AMD women aged <65 years were the carriers of the C/C genotype significantly more frequently than their control counterparts.

Objectives: This study aimed to examine the associations between the fat mass and obesity associated (FTO) gene rs9939609 variant with obesity and metabolic syndrome and interactions between FTO alleles, dietary intake and physical activity in Lithuanian adult population., Study Design: Cross-sectional study., Methods: A health survey was carried out in randomly selected municipalities of Lithuania. The random sample was obtained from the lists of 25-64 year-old inhabitants. The data from 1020 individuals were analyzed. The single-nucleotide polymorphism, rs9939609, in the FTO gene was assessed using a real-time polymerase chain reaction. 24-hour recall was used for evaluation of dietary habits. Information on physical activity at work, traveling to and from work and at leisure time was gathered by a standard questionnaire., Results: The carriers of the AA genotype had the highest mean values of body mass index (BMI) and waist circumference (WC). They had 1.72 time higher odds of obesity (P = 0.009) and 1.67 time higher odds of increased WC (P = 0.013) than those with the TT genotype. Carriers of the T allele had lower prevalence of metabolic syndrome compared to carriers of the AA genotype (33.8% and 42.5% respectively; P = 0.018). No interaction between the rs9939609 variant and energy or dietary intakes on weight status was found. Significant effect of the interactions 'genotype×age' and 'genotype×physical activity' on BMI was demonstrated. The FTO rs9939609 polymorphism was associated with anthropometric parameters and metabolic syndrome in the younger age group (25-44 years) and in individuals having low level of physical activity., Conclusions: Age and physical activity modulated the effect of the FTO polymorphism on weight status and metabolic syndrome in Lithuanian adult population., (Copyright © 2016 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Transforming growth factor (TGF)-β1 is a cytokine that participates in a broad range of cellular regulatory processes and is associated with various diseases including aortic aneurysm. Increased TGF-β1 levels are linked to Marfan syndrome (MFS) caused by fibrillin1 ( FBN1 ) mutations and subsequent defects in signaling system. FBN1 single nucleotide polymorphisms (SNPs) rs2118181 and rs1059177 do not cause MFS but are associated with dilative pathology of aortic aneurysms (DPAAs). TGF-β1 and FBN1 SNPs rs2118181 and rs1059177 are potential biomarkers for early diagnosis of DPAA. We investigated the relationship between TGF-β1 levels in human blood plasma and FBN1 rs2118181 and rs1059177 in 269 individuals. The results showed a quantitative dependence of SNP genotype and TGF-β1 concentration. Presence of a single rs2118181 minor allele (G) increased the amount of TGF-β1 by roughly 1 ng/mL. Two copies of FBN1 rs1059177 minor allele (G) were required to have an additive effect on TGF-β1 levels. We found higher TGF-β1 concentrations in men compared with women ( p = 0.001). A strong correlation between TGF-β1 levels and FBN1 SNPs suggests that a single nucleotide substitution in FBN1 sequence might reduce bioavailability or binding properties of fibrillin-1 and have an effect on TGF-β1 activation and cytokine concentration in blood plasma. By establishing the relationship between TGF-β1 and FBN1 SNPs rs2118181 and rs1059177, we provide evidence that their combination might be used as molecular biomarkers to identify patients at risk for sporadic ascending aortic aneurysm and aortic dissection.

Transforming growth factor β1 (TGF- β1) is a cytokine that participates in a broad range of cellular regulatory processes and is associated with various diseases including aortic aneurysm. Increased TGF- β1 levels are associated with Marfan syndrome (MFS) caused by FBN1 mutations and subsequent defects in signaling system. We studied TGF- β1 levels in 62 patients with sporadic, non syndromic, dilatative pathology of ascending aorta (DPAA) and in reference group subjects (n = 212). An initial screening of 212 reference individuals identified TGF- β1 gender discrepancies and age-dependent cytokine increase in women. Patients with DPAA had increased levels of TGF- β1 in comparison to reference group subjects (median 7.7 ng/ml, range 2.1-25.3, and median 6.2 ng/ml, range 1.0-33.1, respectively). There is a significant association between TGF-β1 concentration and DPAA (OR 1.084, CI 1.027-1.144, p = 0.004) but the mechanisms of cause and effect have not been established yet. Slightly increased TGF-β1 concentrations in patients with sporadic DPAA in comparison to the reference subjects show a potential use of TGF-β1 as a biomarker for the disease. However, cytokine dependence on age, gender, and other unknown factors among individuals with no cardiovascular complains reduces its specificity for DPAA. We would also like to raise awareness regarding the choice of methods when measuring TGF-β1 levels with an emphasis on preanalytical phase and the choice of sample.

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.

Objectives: To investigate polymorphisms of the fibrillin-1 (FBN1) gene (namely, rs2118181, rs1036477, rs10519177, rs755251 and rs4774517) in a case-control study for dilatative pathology of the ascending thoracic aorta (DPATA) from Lithuanians., Methods: We studied 312 patients who had undergone aortic reconstructive surgery for DPATA. These patients were sub-divided according to the phenotypes of their DPATA into (i) ascending aortic aneurysm (n = 160), (ii) post-stenotic dilatation of the ascending aorta due to aortic valve stenosis (n = 79) and (iii) Stanford A dissection (n = 73). The reference group (n = 472) was recruited from a random sample screened within epidemiological studies of the Lithuanian population. FBN1 polymorphisms were studied by real-time polymerase-chain-reaction amplification., Results: Patients within the aortic dissection sub-group had significantly higher minor allele frequencies in all five FBN1 single nucleotide polymorphism (SNPs) studied versus reference group subjects (P < 0.0001). Minor allele frequencies in SNPs rs2118181, rs1036477 were significantly higher in those with aortic aneurysm when compared with the reference group (P = 0.007). Thus, minor alleles of FBN1 SNPs studied were significantly associated with aortic dissection with odds ratios (ORs) 2.59-2.13, P < 0.001, while SNPs rs2118181 and rs1036477 with an increased risk of ascending aortic aneurysm [OR 1.67, confidence interval (CI) 95% 1.61-2.40]. The association of FBN1 genotypes with each phenotype of DPATA was assessed using logistic regression models adjusted for gender, age and hypertension. The additive model best fitted SNPs rs2118181 and rs1036477 in association with the ascending aortic aneurysm sub-group (OR 1.70, CI 95% 1.17-2.46) or the Stanford A dissection sub-group (OR 2.64, CI 95% 1.66-4.19). A recessive model fitted best the association between SNPs rs10519177, rs755251, rs4774517 and Stanford A dissection (OR 4.31, CI 95% 2.06-9.01). There were no significant associations between all studied FBN1 SNPs and post-stenotic or bicuspid aortic dilatation., Conclusions: Our study provides evidence for the following: (i) FBN1 SNPs rs2118181, rs1036477, rs10519177, rs4774517, rs755251 may increase susceptibility to aortic dissections and (ii) FBN1 SNPs rs2118181, rs1036477 to the formation of aortic aneurysms. Thus, these SNPs might be considered as biomarkers for identifying patients at risk for ascending aortic aneurysm and aortic dissection., (© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)