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Apch 2017 Delegates' Abstract

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Apch 2017 Delegates' Abstract APCH 2017 DELEGATES’ ABSTRACT Topic: Basic Science: Genetics, genomics, proteomics and metabolomics Abstract No: 3630 A PILOT GENOME WIDE ASSOCIATION STUDY (GWAS) IN MULTI ETHNIC POPULATION OF MALAYSIA Ms Syahirah Kaja Mohideen*1 ; Prof Datuk Dr A Rahman A Jamal1 ; Prof Dr Nor Azmi Kamaruddin1 ; Prof Dr Norlela Sukor1 ; Ms Elena Aisha Azizan1 1MEDICINE/ UNIVERSITI KEBANGSAAN MALAYSIA (UKM)/ Malaysia Objective Primary aldosteronism (PA) occurs due to the presence of aldosterone-producing lesions commonly located in the adrenal gland which can thus be cured by an adrenalectomy. Studies on surgically removed tissues found somatic mutations in five genes (KCNJ5, ATP1A1, ATP2B3, CACNA1D, and CTNNB1) can cause the excess aldosterone production. Most of these studies were performed in Caucasian patients. The aim of our study is to understand the genetic background which may promote somatic mutation in these genes and to investigate the frequency and distribution of these somatic mutations in the multiethnic Asian population in Malaysia. Method To characterize the genetic background of PA, a pilot genome wide association study (GWAS) was performed using the Human Infinium OmniExpressExome-8 v1.4 BeadChip containing 960,919 markers to compare gDNA of PA patients with healthy controls. The Association Workflow in Partek® Genomics SuiteTM was used for quality control and association analysis was performed using the Chi-square Test and reported as an odds ratio (OR). On tumour DNA, targeted sequencing of hotspots for the five causal genes were performed. Discussion From the pilot GWAS, two SNPs in chromosome 2 were identified to be associated with PA (OR=11.03, P-value=7.1x10-10, and OR=1.61, P-value=4.0x10-9,). One of the SNP is within a gene, EPHA4. Interestingly EPHA4 is known to bind to Efnb3 which when knockedout in mice, causes enhanced constriction in the carotid arteries (Wang et al., 2016). As for prevalence of somatic mutations in the multiethnic population of Malaysia, the most prevalent somatic mutation is the KCNJ5 G151R mutation (76% of aldosterone-producing lesions). Conclusion The highest number observed in Chinese patients (91%), followed by Malay patients (67%). To note, unlike previous findings in Caucasian cohorts, KCNJ5 mutation were present equally in males and females (75% and 78%) with an average age of 56±14 years old. Keywords: PRIMARY ALDOSTERONISM, GENOME WIDE ASSOCIATION STUDY, SOMATIC MUTATION, ALDOSTERONE- PRODUCING ADENOMAS Topic: Basic Science: Genetics, genomics, proteomics and metabolomics Abstract No: 3636 Altered expression profile of IL6/STAT3-pathway genes in patients with essential hypertension in very old age Vera Erdman*1 ; Timur Nasibullin1 ; Ilsiar Tuktarova1 ; Yanina Timasheva1 ; Olga Mustafina1 1Department of physiological genetics/ Institute of Biochemistry and Genetics / Russian Federation Objective Essential hypertension (EH) is one of the most common diseases the elderly. Genetic predisposition to EH is undoubted and its influence is increased with age. Transcriptional activity (TA) of some genes was also demonstrated to decline in age-depended fashion in general population and in diseased individuals. Therefore, we considered it interesting to evaluate TA of IL6/STAT3- pathway genes, disturbance in functioning of which leads to development of inflammation and disease formation. Our aim was to study the expression profile of IL6/STAT3-pathway genes in healthy individuals and in patients with EH. Method All participants were women aged between 80 and 100, residents of the Republic of Bashkortostan (Russia). EH patients didn't receive antihypertensive treatment at the time of blood collection. Total RNA was isolated from peripheral blood leukocytes. The analysis of gene transcriptional activity was performed using IL6/STAT3 Signaling Pathway RT² Profiler PCR Array. ΔΔCt-method was applied to analyze the experimental data. Discussion We found that expression levels of NFKB1 and IL18R1 genes were increased, and CCL5, CSF1, CD4, RPLP0, BCL2, SRC, IL15, CD40LG, CFS3, CDKN1A, MYC and CFS2 genes were down-regulated in patients compared to healthy individuals. Differentially expressed genes are involved in a wide range of biological processes and some signaling pathways, such as inflammatory response, apoptotic regulation, senescence, immune response, response to stimulus, cellular defense response, cytokine-mediated signaling pathway, NF-kappaB-signaling. Conclusion The results of our study indicate that IL6/STAT3-pathway genes may be implicated in the pathogenesis of hypertension in very old age. Keywords: essential hypertension; gene expression; IL6/STAT3-pathway; aging Topic: Basic Science: Genetics, genomics, proteomics and metabolomics Abstract No: 3811 The European contribution to inheritance EH and genetic pool in Uzbek population Aleksandr Nagay*1 1Department of Arterial Hypertension and Molecular Genetics Research / Republican Specialized Center of Cardiology/ Uzbekistan (Oʻzbekiston) Objective To study of familial character of essential hypertension (EH) and to evaluate the role of genetic pool. Method The study included 100 healthy volunteers and 312 patients with I-II grade of EH. For linkage disequilibrium research, have been taken microsatellite SSR-markers. Discussion We have studied genotype of 20 gene of cardiovascular continuum and identified 12 diagnostically significant genes. Registration of the genotyping results has identified an association SNP genes (ETA ENDRA T/T; ADDUCIN G/G; GNB3 С/C; ACE D/D; CYP11B2 T/T) with the risk of violations of water-salt metabolism, (PPR2Y P/P; ADRB3 T/T, AGTR1 A/A, AGTR2 G/G; β2-AR G/G) with the risk of metabolic syndrome, ENDOTHEL system genes (B2BKR +9-+9; eNOS; 4a/4b) with the risk of endothelial dysfunction. The heritage of hypertension in Uzbek population is estimated as: 17% of east, 33% of the western, 25% from the central Europe, 8% for Anatolia and 17% for Southeast Asia. In the analysis of mtDNA HVI region in patients with EH, we have identified six common point of nucleotide substitutions (H, T, X, I, V, L3). Comparative analysis of HVI region of mtDNA and SNP C344T in hypertension candidate gene CYP11B2, showed a definite connection with carriage of "negative" TT genotype of CYP11B2 gene with substitution in 16327 loci of HVI (OR-2,7; 95%CI-0,32-23,14). Detected N, R, J-superclusters in the Uzbek population date back to the alleged place of occurrence of the territories of South-East Asia and Western Europe. We calculated the genetic distance and determined that differences in the genome is 9-61%. We have determined that monogenic Western and hybrid Eastern population of Uzbekistan are often carriers of damaging DD -genotype of ACE gene localized in chromosome-17. Conclusion The functional significance of 12 genes in Uzbek population with a combination of atherosclerosis and metabolic syndrome is similar 83% in most of European heritage type of hypertension. However, a distinctive sensitivity to the exchange of sodium in these individuals is due to 17% of the Asian contribution. Keywords: mtDNA, Linkage disequilibrium, SNP, Essential hypertension Topic: Basic Science: Genetics, genomics, proteomics and metabolomics Abstract No: 4772 α-Adducin Gene Promoter DNA Methylation and the Risk of Essential Hypertension Hamdy Omar*1 ; Mohamed El-shabrawi; Ola Leheta; Nervana Bayoumy 1Department of medicine/ Faculty of medicine, Suez canal university/ Egypt, Arab Rep. Objective This study was conducted to test the association between promoter DNA methylation of α-adducin (ADD1) gene and the risk of essential hypertension (EH). Method A total of a 150 EH patients and 100 aged and gender matched controls were investigated. DNA methylation levels of five CpG dinucleotides on ADD1 promoter were measured employing bisulphate pyrosequencing technology. Discussion Our results showed that females have a higher ADD1 DNA methylation than males and a significantly lower CpG1 methylation level is associated with increased risk of EH among them. As for males, a significant association between lower CpG2-5 methylation levels and increased risk of EH was shown. In addition, CpG2-5 methylation was found to be a highly significant predictor for EH among male. In females, CpG1 methylation was considered a predictor of hypertension. No significant correlations were found with biochemical measures, apart from the concentration of aspartate aminotransferase (AST) which was inversely correlated with ADD1 CpG2-5 methylation levels among female controls (r= -0.703). Conclusion These findings highlight that ADD1 methylation may have a contributing role in the pathogenesis of EH with varying implications for both genders. Topic: Basic Science: Genetics, genomics, proteomics and metabolomics Abstract No: 4917 THE INVOLVEMENT OF KIDNEY DNA METHYLATION IN BLOOD PRESSURE REGULATION. Ingrid Wise*1 ; Priscilla Prestes1 ; Maciej Tomaszewksi2 3 ; Fadi Charchar1 4 1Faculty of Science and Technology/ Federation University Australia/ Australia, 2Department of Cardiovascular Sciences/ University of Leicester/ United Kingdom, 3Faculty of Human and Medical Sciences/ University of Manchester/ United Kingdom, 4Department of Physiology/ University of Melbourne/ Australia Objective Increasing evidence suggests that epigenetic modifications such as DNA methylation (5mC) is important to the development of essential hypertension, and that changes in DNA methylation of blood cells is associated to blood pressure (BP). So far there has been no studies of epigenetic changes in the
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