A genome-wide association study reveals susceptibility loci for myocardial infarction/coronary artery disease in Saudi Arabs

Wakil, Salma M.; Ramesh, Ram; Muiya, Nzioka P.; Mehta, Munish; Andres, Editha; Mazhar, Nejat; Baz, Batoul; Hagos, Samya; Alshahid, Maie; Meyer, Brian F.; Morahan, Grant; Dzimiri, Nduna

doi:10.1016/j.atherosclerosis.2015.11.019

Cited by 62 publications

(59 citation statements)

References 50 publications

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“…In contrast, Kcne2 deletion was cardioprotective, reducing infarct size and cardiac tissue damage, in mice following a lower ligation of the coronary artery designed to promote infarct but a lesser degree of early arrhythmogenesis [15]. Kcne2 is ubiquitously expressed, in the heart but also pancreatic islet cells, gastric parietal cells, the thyroid and other epithelia, and its deletion also causes diabetes, atherosclerosis and fatty liver in mice [16, 38–42]; Kcne2 polymorphisms also influence risk if coronary artery disease in human populations [43, 44]. Thus, even monogenic arrhythmia syndromes can exhibit complex pathogenesis and opposite outcomes depending on the nature of the cardiac ischemic insult, for example.…”

Section: Discussionmentioning

confidence: 99%

Remote ischemic preconditioning differentially attenuates post-ischemic cardiac arrhythmia in streptozotocin-induced diabetic versus nondiabetic rats

Zhang

Liu

et al. 2017

Cardiovasc Diabetol

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BackgroundSudden cardiac death (SCD), a leading cause of global mortality, most commonly arises from a substrate of cardiac ischemia, but requires an additional trigger. Diabetes mellitus (DM) predisposes to SCD even after adjusting for other DM-linked cardiovascular pathology such as coronary artery disease. We previously showed that remote liver ischemia preconditioning (RLIPC) is highly protective against cardiac ischemia reperfusion injury (IRI) linked ventricular arrhythmias and myocardial infarction, via induction of the cardioprotective RISK pathway, and specifically, inhibitory phosphorylation of GSK-3β (Ser 9).MethodsWe evaluated the impact of acute streptozotocin-induced DM on coronary artery ligation IRI-linked ventricular arrhythmogenesis and RLIPC therapy in rats.ResultsPost-IRI arrhythmia induction was similar in nondiabetic and DM rats, but, unexpectedly, DM rats exhibited lower incidence of SCD during reperfusion (41 vs. 100%), suggesting uncontrolled hyperglycemia does not acutely predispose to SCD. RLIPC was highly effective in both nondiabetic and DM rats at reducing incidence and duration of, and increasing latency to, all classes of ventricular tachyarrhythmias. In contrast, atrioventricular block (AVB) was highly responsive to RLIPC in nondiabetic rats (incidence reduced from 72 to 18%) but unresponsive in DM rats. RISK pathway induction was similar in nondiabetic and DM rats, thus not explaining the DM-specific resistance of AVB to therapy.ConclusionsOur findings uncover important acute DM-specific differences in responsiveness to remote preconditioning for ventricular tachyarrhythmias versus AVB, which may have clinical significance given that AVB is a malignant arrhythmia twofold more common in human diabetics than nondiabetics, and correlated to plasma glucose levels >10 mmol/L.

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Section: Discussionmentioning

confidence: 99%

Remote ischemic preconditioning differentially attenuates post-ischemic cardiac arrhythmia in streptozotocin-induced diabetic versus nondiabetic rats

Zhang

Liu

et al. 2017

Cardiovasc Diabetol

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“…Known genetic variants in DMRs. Two of the twelve DMRs common in trans-ancestry SBP and DBP analysis, TFAP2D and HLX, contain SNPs previously associated with blood pressure [17,18]. The genetic variant in the PDZD2 DMR was previously associated with myocardial infarction [18].…”

Section: Overlap For Trans-ancestrymentioning

confidence: 99%

Associations between high blood pressure and DNA methylation

et al. 2020

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BackgroundHigh blood pressure is a major risk factor for cardiovascular disease and is influenced by both environmental and genetic factors. Epigenetic processes including DNA methylation potentially mediate the relationship between genetic factors, the environment and cardiovascular disease. Despite an increased risk of hypertension and cardiovascular disease in individuals of South Asians compared to Europeans, it is not clear whether associations between blood pressure and DNA methylation differ between these groups. MethodsWe performed an epigenome-wide association study and differentially methylated region (DMR) analysis to identify DNA methylation sites and regions that were associated with systolic blood pressure, diastolic blood pressure and hypertension. We analyzed samples from 364 European and 348 South Asian men (first generation migrants to the UK) from the Southall And Brent REvisited cohort, measuring DNA methylation from blood using the Illumina Infinium ® HumanMethylation450 BeadChip. ResultsOne CpG site was found to be associated with DBP in trans-ancestry analyses (i.e. both ethnic groups combined), while in Europeans alone seven CpG sites were associated with DBP. No associations were identified between DNA methylation and either SBP or hypertension. Comparison of effect sizes between South Asian and European EWAS for DBP, SBP and hypertension revealed little concordance between analyses. DMR analysis identified several regions with known relationships with CVD and its risk factors.

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“…A GWAS of MI and coronary artery disease (CAD) in a Saudi Arab population identified an intergenic variant, rs7421388, near PLCL1 associated with CAD ( P = 4.31 × 10 -6 ) and replicated in an independent sample of Saudi Arabs ( P = 5.37 × 10 -7 ). (34) In another study of an ethnic Arab population, rs1147169 in PLCL1 was protective against a low level of high density lipoprotein-cholesterol levels ( P = 2.87 × 10 -7 ). (35) In individuals of European ancestry, rs988583 and rs1147169 are in linkage equilibrium (R 2 = 0.0043).…”

Section: Discussionmentioning

confidence: 97%

Genetic loci associated with prevalent and incident myocardial infarction and coronary heart disease in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium

Hahn

Brown

et al. 2020

Preprint

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64Background 65 Genome-wide association studies have identified multiple genomic loci associated with coronary artery 66 disease, but most are common variants in non-coding regions that provide limited information on causal 67 genes and etiology of the disease. To better understand etiological pathways that might lead to discovery 131 Houston (21); SHIP was called in Illumina GenomeStudio using the CHARGE Consortium joint calling 132 cluster file; GeneSTAR used the Illumina GenomeStudio and zCall software (22); and WGHS data was 133 called using the Illumina BeadStudio v.3.3. Variant quality control (QC) was performed centrally (21) 134 and by the individual studies, including checking concordance with previous GWAS data, and excluding 135 participants with missing >5% genotypes, population clustering outliers, individuals with high inbreeding 136 coefficients or heterozygote rates, gender mismatches, duplicated pairs, and unexpectedly high proportion 137 of identity-by-descent sharing for family studies.

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A genome-wide association study reveals susceptibility loci for myocardial infarction/coronary artery disease in Saudi Arabs

Cited by 62 publications

References 50 publications

Remote ischemic preconditioning differentially attenuates post-ischemic cardiac arrhythmia in streptozotocin-induced diabetic versus nondiabetic rats

Remote ischemic preconditioning differentially attenuates post-ischemic cardiac arrhythmia in streptozotocin-induced diabetic versus nondiabetic rats

Associations between high blood pressure and DNA methylation

Genetic loci associated with prevalent and incident myocardial infarction and coronary heart disease in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium

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