Niels Grote Beverborg, M Abdullah Said, Haye H van der Wal, Niek Verweij, Peter van der Meer, Pim van der Harst
The observation that premenopausal women have a relatively low incidence of heart disease led in the nineteen eighties to the hypothesis that iron deficiency protects against heart diseases. These early observations were followed-up by conflicting epidemiological data. To confer causal relationships from epidemiological data is challenging as results can be influenced by residual confounding or reverse causation. For bias reduction, an alternative analysis strategy utilizing single-nucleotide polymorphisms (SNPs) as instrumental variables (Mendelian Randomization) has been developed...
January 12, 2020: Circulation. Genomic and Precision Medicine
Martina Olsson Lindvall, Marcela Davila Lopez, Sofia Klasson, Lena Hansson, Staffan Nilsson, Tara M Stanne, Christina Jern
Characterizing the relationship between genetic, epigenetic (e.g., deoxyribonucleic acid [DNA] methylation), and transcript variation could provide insights into mechanisms regulating hemostasis and potentially identify new drug targets. Several hemostatic factors are synthesized in the liver, yet high-resolution DNA methylation data from human liver tissue is currently lacking for these genes. Single-nucleotide polymorphisms (SNPs) can influence DNA methylation in cis which can affect gene expression. This can be analyzed through allele-specific methylation (ASM) experiments...
December 30, 2019: Thrombosis and Haemostasis
Jian-Li Li, Liu-Yu Liu, Dong-Dong Jiang, Yi-Ying Jiang, Guo-Qiu Zhou, Dong-Can Mo, Man Luo
BACKGROUND: Previous genome-wide association studies have found two single nucleotide polymorphisms (SNP) rs7692387 and rs1842896 located on or near the GUCY1A3 gene were associated with coronary artery disease (CAD). GUCY1A3 was considered to be involved in the process of atherosclerosis, but there was little information about the association between genotypic polymorphisms of the GUCY1A3 and large artery atherosclerotic (LAA) stroke. This study aimed to investigate the associations between the GUCY1A3 rs7692387, rs1842896 polymorphisms and LAA stroke susceptibility...
December 28, 2019: Lipids in Health and Disease
Ningda Xu, Hui Xu, Mingwei Zhao, Yongsheng Xu, Lvzhen Huang
BACKGROUND: To investigate the association of systemic, serum lipids and genetic variants in the high-density lipoprotein (HDL) metabolic pathway with polypoidal choroidal vasculopathy (PCV) in China. METHODS: The case-control study was included 150 controls and 66 cases with PCV. Serum levels of total cholesterol (TC), low-density lipoprotein (LDL), HDL, triglycerides (TG), apolipoprotein A1 (APOA1), apolipoprotein B (APOB) together with systemic risk factors including gender, hyperlipidemia, diabetes mellitus (DM), hypertension, coronary artery disease (CAD) and asthma were identified...
2019: PloS One
Liu Miao, Guo-Xiong Deng, Rui-Xing Yin, Rong-Jun Nie, Shuo Yang, Yong Wang, Hui Li
BACKGROUND: Although many observational studies have shown an association between plasma homocysteine levels and cardiovascular diseases, controversy remains. In this study, we estimated the role of increased plasma homocysteine levels on the etiology of coronary heart disease and acute myocardial infarction. METHODS: A two-sample Mendelian randomization study on disease was conducted, i.e. "coronary heart disease" ( n  = 184,305) and "acute myocardial infarction" ( n  = 181,875)...
December 16, 2019: European Journal of Preventive Cardiology
Shuai Yuan, Magnus Bäck, Maria Bruzelius, Amy M Mason, Stephen Burgess, Susanna Larsson
Whether circulating fatty acids (FAs) play a causal role in the development of cardiovascular disease (CVD) remains unclear. We conducted a Mendelian randomisation study to explore the associations between plasma phospholipid FA levels and 15 CVDs. Summary-level data from the CARDIoGRAMplusC4D, MEGASTROKE, and Atrial Fibrillation consortia and UK Biobank were used. Sixteen single-nucleotide polymorphisms (SNPs) associated with ten plasma FAs were used as instrumental variables. SNPs in or close to the FADS1 gene were associated with most FAs...
December 7, 2019: Nutrients
Zhaoqing Sun, Shuchao Pang, Yinghua Cui, Bo Yan
Background: Acute myocardial infarction (AMI) which is a specific type of coronary artery disease (CAD), is caused by the combination of genetic factors and acquired environment. Although some common genetic variations have been recorded to contribute to the development of CAD and AMI, more genetic factors and potential molecular mechanisms remain largely unknown. The GATA6 gene is expressed in the heart during embryogenesis and is also detected in vascular smooth muscle cells (VSMCs), different human primary endothelial cells (ECs), and vascular ECs in mice...
2019: Frontiers in Genetics
Mall Eltermaa, Maili Jakobson, Meeme Utt, Sulev Kõks, Reedik Mägi, Joel Starkopf
OBJECTIVE: Coronary artery disease contributes to noncommunicable disease deaths worldwide. In order to make preventive methods more accurate, we need to know more about the development and progress of this pathology, including the genetic aspects. Humanin is a small peptide known for its cytoprotective and anti-apoptotic properties. Our study looked for genomic associations between humanin-like nuclear isoform genes and coronary artery disease using CARDIoGRAMplusC4D Consortium data...
November 21, 2019: BMC Research Notes
Rebecca N Mitchell, Foram N Ashar, Marjo-Riitta Jarvelin, Philippe Froguel, Nona Sotoodehnia, Jennifer A Brody, Sylvain Sebert, Heikki Huikuri, John Rioux, Philippe Goyette, Charles E Newcomb, M Juhani Junttila, Dan E Arking
Background Sudden cardiac death (SCD) accounts for ≈300 000 deaths annually in the United States. Men have a higher risk of SCD and are more likely to have underlying coronary artery disease, while women are more likely to have arrhythmic events in the setting of inherited or acquired QT prolongation. Moreover, there is evidence of sex differences in the genetics of QT interval duration. Using sex- and coronary artery disease-stratified analyses, we assess differences in genetic association between longer QT interval and SCD risk...
December 3, 2019: Journal of the American Heart Association
Haihua Wang, Shufang Zhang, Na Wang, Jie Zhang, Mingkai Chen, Xiaohui He, Yinghua Cui, Shuchao Pang, Bo Yan
BACKGROUND: Coronary artery disease (CAD) including acute myocardial infarction (AMI) is a common complex disease caused by atherosclerosis. Vascular epithelial growth factor receptor-1 (VEGFR-1) stimulates angiogenesis and vascular permeability, and functions as a decoy to sequester VEGF and prevent initiation of intracellular signaling. VEGFR-1 knockout mice exhibit significantly higher mortality due to heart failure, cardiac hypertrophy, and cardiac dysfunction. An evident increase in macrophage infiltration and cardiac fibrosis are also observed after transverse aortic constriction...
November 19, 2019: Human Genomics
Chengqian Dai, Shu-Jui Kuo, Sung-Lin Hu, Chun-Hao Tsai, Yuan-Li Huang, Chien-Chung Huang, Lihong Wang, Guohong Xu, Chen-Ming Su, Chih-Hsin Tang
Vascular endothelial growth factor C (VEGF-C) promotes angiogenesis, a prominent feature in rheumatoid synovitis, contributing to the perpetuation of the global burden of rheumatoid arthritis (RA). VEGF-C gene polymorphisms predict the risk of developing various human diseases, such as urothelial cell carcinoma, oral cancer and coronary artery disease. We sought to determine whether single nucleotide polymorphisms (SNPs) of the VEGF-C gene can predict the risk of RA. Our study recruited 210 patients with RA and 373 healthy controls between 2007 and 2015, and performed comparative genotyping for SNPs rs7664413, rs11947611, rs1485766, rs2046463 and rs3775194...
2019: International Journal of Medical Sciences
Hao Qiu, Zheng Chen, Lu Lv, Weifeng Tang, Rong Hu
Coronary artery disease (CAD), a common cardiovascular disease, has become a vital cause of mortality worldwide. Genetic microRNA ( miR ) polymorphisms might contribute to CAD susceptibility. In this study, we selected miR-146a , miR-196a2 , and miR-499 single nucleotide polymorphisms and conducted a case-control study. In total, 505 CAD cases and 1109 controls were recruited. We used SNPscan™ genotyping assay to obtain genotyping of miR rs2910164, rs11614913, and rs3746444 variants. We found that miR-196a2 rs11614913 T > C decreased the susceptibility of myocardial infarction (MI) (TC vs...
November 6, 2019: DNA and Cell Biology
C Mary Schooling, Glen D Johnson, Jean Grassman
Lead is pervasive, although lead exposure has fallen in response to public health efforts. Observationally, lead is positively associated with cardiovascular disease and hypertension. We used separate-sample instrumental variable analysis with genetic instruments (Mendelian randomization) based on 13 single nucleotide polymorphisms (SNP), from a genome wide association study, strongly (p-value < 5 × 10-6 ) and independently associated with blood lead. These SNPs were applied to a large extensively genotyped coronary artery disease (CAD) study (cases = <76014, controls = <264785) largely based on CARDIoGRAPMplusC4D 1000 Genomes and the UK Biobank SOFT CAD, to the UK Biobank (n = 361,194) for blood pressure and to the DIAGRAM 1000 genomes diabetes case (n = 26,676)-control (n = 132,532) study...
November 5, 2019: Scientific Reports
Simin Jafaripour, Payam Sasanejad, Malihe Dadgarmoghaddam, Ariane Sadr-Nabavi
Coronary artery disease (CAD) and ischemic stroke (IS) are commonly considered distinct disease phenotypes. However, there is some evidence in favor of a degree of overlap between genetic susceptibility to CAD and genetic risk factors for IS. In the present study, we aimed to examine the role of two single-nucleotide polymorphisms (SNPs), rs3825807 and rs11556924, located in the ADAMTS7 and ZC3HC1 genes, respectively, associated with CAD in published GWASs in European populations and their possible contribution to the development of coronary atherosclerosis and cerebral LA atherosclerosis in a case-control study of an the Iranian population...
2019: Critical Reviews in Eukaryotic Gene Expression
Wole Akosile, Joanne Voisey, Bruce Lawford, David Colquhoun, Ross McD Young, Divya Mehta
BACKGROUND: Previous studies have established that coronary artery disease is associated with excess inflammation. These studies have shown an elevation of both pro and anti-inflammatory cytokines in sufferers of coronary artery disease. There is increasing interest in the role played by the inflammasome Nod Like Receptor family pyrin domain containing 3 (NLRP3) in the aetiology of coronary artery disease. Increased severity of coronary artery disease correlates with higher levels of expression of NLRP3...
October 19, 2019: Gene
Yang Li, Han Yan, Jian Guo, Yingchun Han, Cuifang Zhang, Xiuying Liu, Jie Du, Xiao-Li Tian
AIMS: Genetic contribution to coronary artery disease (CAD) remains largely unillustrated. Although transcriptomic profiles have identified dozens of genes that are differentially expressed in normal and atherosclerotic vessels, whether those genes are genetically associated with CAD remains to be determined. Here, we combined genetic association studies, transcriptome profiles and in vitro and in vivo functional experiments to identify novel susceptibility genes for CAD. METHODS AND RESULTS: Through an integrative analysis of transcriptome profiles with genome-wide association studies for CAD, we obtained 18 candidate genes and selected one representative SNP for each gene for multi-centered validations...
October 12, 2019: Cardiovascular Research
V Eric Kerchberger, Yi Huang, Tatsuki Koyama, M Benjamin Shoemaker, Dawood Darbar, Julie A Bastarache, Lorraine B Ware, Ciara M Shaver
OBJECTIVES: New-onset atrial fibrillation during critical illness is an independent risk factor for mortality. The ability to identify patients at high risk for new-onset atrial fibrillation is limited. We hypothesized that genetic susceptibility contributes to risk of new-onset atrial fibrillation in the ICU. DESIGN: Retrospective sub-study of a prospective observational cohort study. SETTING: Medical and general surgical ICUs in a tertiary academic medical center...
January 2020: Critical Care Medicine
Abirami Veluchamy, Lucia Ballerini, Veronique Vitart, Katharina E Schraut, Mirna Kirin, Harry Campbell, Peter K Joshi, Devanjali Relan, Sarah Harris, Ellie Brown, Suraj S Vaidya, Baljean Dhillon, Kaixin Zhou, Ewan R Pearson, Caroline Hayward, Ozren Polasek, Ian J Deary, Thomas MacGillivray, James F Wilson, Emanuele Trucco, Colin N A Palmer, Alexander S F Doney
OBJECTIVE: The retina may provide readily accessible imaging biomarkers of global cardiovascular health. Increasing evidence suggests variation in retinal vascular traits is highly heritable. This study aimed to identify the genetic determinants of retinal vascular traits. Approach and Results: We conducted a meta-analysis of genome-wide association studies for quantitative retinal vascular traits derived using semi-automatic image analysis of digital retinal photographs from the GoDARTS (Genetics of Diabetes Audit and Research in Tayside; N=1736) and ORCADES (Orkney Complex Disease Study; N=1358) cohorts...
December 2019: Arteriosclerosis, Thrombosis, and Vascular Biology
Chuanlong Fan, Tao Huang, Xuejun Kong, Xiaohong Zhang, Zuquan Zou, Jing Xiao
Although a large body of literature reported that high intake of vitamin E played a possible role in reducing risk of cardiometabolic diseases, conflicting results were also found in some observational studies due to confounding factors. Hence, we used a Mendelian randomization study as an alternative way to examine the causality between circulating vitamin E and cardiometabolic diseases. Summary-level data were extracted from consortia and three single nucleotide polymorphisms were used as instrumental variables...
September 2019: Journal of Clinical Biochemistry and Nutrition
Tomasz Iwanicki, Anna Balcerzyk, Paweł Niemiec, Wanda Trautsolt, Władysław Grzeszczak, Anna Ochalska-Tyka, Jolanta Krauze, Tomasz Nowak, Iwona Żak
Polymorphic variants of the CYP7A1 gene can increase the risk of atherosclerosis-based coronary artery disease (CAD) and modify serum lipid markers. Method: We studied haplotype-tagging single nucleotide polymorphisms of CYP7A1 in the Caucasian population and if they are associated with CAD, its symptoms, and any of its risk factors. Results: We did not find the genetic variants of CYP7A1 to be associated with an increased risk of CAD. However, we did find that the common rs3808607 variant is associated with modified concentrations of serum total cholesterol and LDL...
October 3, 2019: Biomarkers in Medicine
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