Genetic copy number variants in myocardial infarction patients with hyperlipidemia

<p>Abstract</p> <p>Background</p> <p>Cardiovascular disease is the chief cause of death in Taiwan and many countries, of which myocardial infarction (MI) is the most serious condition. Hyperlipidemia appears to be a significant cause of myocardial infarction, because it causes atherosclerosis directly. In recent years, copy number variation (CNV) has been analyzed in genomewide association studies of complex diseases. In this study, CNV was analyzed in blood samples and SNP arrays from 31 myocardial infarction patients with hyperlipidemia.</p> <p>Results</p> <p>We identified seven CNV regions that were associated significantly with hyperlipidemia and myocardial infarction in our patients through multistage analysis (P<0.001), at 1p21.3, 1q31.2 (<it>CDC73</it>), 1q42.2 (<it>DISC1</it>), 3p21.31 (<it>CDCP1</it>), 10q11.21 (<it>RET</it>) 12p12.3 (<it>PIK3C2G</it>) and 16q23.3 (<it>CDH13</it>), respectively. In particular, the CNV region at 10q11.21 was examined by quantitative real-time PCR, the results of which were consistent with microarray findings.</p> <p>Conclusions</p> <p>Our preliminary results constitute an alternative method of evaluating the relationship between CNV regions and cardiovascular disease. These susceptibility CNV regions may be used as biomarkers for early-stage diagnosis of hyperlipidemia and myocardial infarction, rendering them valuable for further research and discussion.</p

Shorter GT repeats in the heme oxygenase-1 gene promoter are associated with a lower severity score in coronary artery disease

Abstract Background: The glutathione thymidine repeats [(GT) n ] of the heme oxygenase (HO)-1 gene promoter have been shown to be correlated with the incidence of coronary artery disease (CAD), patients with shorter repeats being less likely to have CAD. In this study, we investigated whether (GT) n repeats in the HO-1 promoter were related to a quantitative angiographic severity of CAD. Methods: The allele frequency of the HO-1 gene promoter (GT) n repeats was examined in CAD patients with de novo lesions (n ¼ 328). Patients&apos; baseline coronary severity was quantified using the Jeopardy scoring system. Results: The allele frequency of GT repeats in the HO-1 gene promoter had bimodal peaks at (GT) 23 and (GT) 30. Therefore, we defined allele classes as follows: S allele (&lt;23 repeats), M allele (23e29 repeats), and L allele (!30 repeats). The group with severe CAD (Jeopardy score !8) had a significantly lower frequency of the S allele (3.7% vs. 8.9%; p ¼ 0.042) than the group with moderate CAD (Jeopardy score &lt;8). None of the patient with the highest score of 12 (n ¼ 17) carried the class S allele. In a multivariate binary logistic analysis, being a carrier of shorter GT repeats was a significant negative predictor (odds ratio 0.393; p ¼ 0.024) of a higher Jeopardy score grade of CAD. Conclusion: Our study showed that shorter (GT) n repeat in the HO-1 gene promoter were associated with a lower Jeopardy severity score in patients with significant CAD

Stent implantation for a totally occluded right coronary artery in a six-year-old boy after Kawasaki disease: a case report

<p>Abstract</p> <p>Introduction</p> <p>Coronary stenting has previously been considered to be less feasible in children under 12 years old due to the limitation of vascular access. We report the case of a six-year-old boy who successfully underwent stent implantation for his totally occluded right coronary artery.</p> <p>Case presentation</p> <p>A Taiwanese boy aged six years and nine months old was found to have giant aneurysms after an acute episode of Kawasaki disease. An angiography revealed that his middle right coronary artery was totally occluded. A 0.014-inch guidewire was advanced to cross the totally occluded site. After pre-dilating the middle portion of his right coronary artery with a 1.5 mm balloon, stenting of his right coronary artery was accomplished using a 2.5 × 28 mm and a 2.5 × 18 mm bare metal stent. A final angiography demonstrated no residual stenosis or dissection.</p> <p>Conclusion</p> <p>Coronary stenting could be a therapeutic option for children as young as six years old. Close follow-up is mandatory because the long-term outcome is still unclear, especially in a small child.</p

The Chromosome 9p21 Variant Not Predicting Long-Term Cardiovascular Mortality in Chinese with Established Coronary Artery Disease: An Eleven-Year Follow-Up Study

Introduction. We examined whether the variant at chromosome 9p21, rs4977574, was associated with long-term cardiovascular mortality in Han Chinese patients with coronary artery disease (CAD). Methodology. Subjects who underwent coronary angiography for chest pain were consecutively enrolled. Fasting blood samples were collected for laboratory and genotype assessments. The information was correlated with data collected from the national death database. Results. There were 925 cases with CAD and 634 without CAD enrolled in the present study. The G allele conferred a significant increase in risk of CAD (odds ratio = 1.47, P=0.003 in the dominant model; odds ratio = 1.36, P=0.018 in the recessive model). During a median of 11 years (inter-quartile range between 5.2 and 12.5 years) of follow-up, neither the total nor the cardiovascular mortality was different among CAD subjects with different genotypes. Using Cox regression analysis, genotypes of rs4977574 still failed to predict cardiovascular mortality (hazard ratio = 1.25, P=0.138 in the dominant model; hazard ratio = 1.05, P=0.729 in the recessive model). Conclusions. The rs4977574 at chromosome 9p21 is associated with presence of CAD in Han Chinese. However, rs4977574 could not predict cardiovascular mortality in these CAD subjects during the eleven-year period of the study

Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels

Large-scale meta-analyses of genome-wide association studies (GWAS) have identified >175 loci associated with fasting cholesterol levels, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). With differences in linkage disequilibrium (LD) structure and allele frequencies between ancestry groups, studies in additional large samples may detect new associations. We conducted staged GWAS meta-analyses in up to 69,414 East Asian individuals from 24 studies with participants from Japan, the Philippines, Korea, China, Singapore, and Taiwan. These meta-analyses identified (P < 5 × 10-8) three novel loci associated with HDL-C near CD163-APOBEC1 (P = 7.4 × 10-9), NCOA2 (P = 1.6 × 10-8), and NID2-PTGDR (P = 4.2 × 10-8), and one novel locus associated with TG near WDR11-FGFR2 (P = 2.7 × 10-10). Conditional analyses identified a second signal near CD163-APOBEC1. We then combined results from the East Asian meta-analysis with association results from up to 187,365 European individuals from the Global Lipids Genetics Consortium in a trans-ancestry meta-analysis. This analysis identified (log10Bayes Factor ≥6.1) eight additional novel lipid loci. Among the twelve total loci identified, the index variants at eight loci have demonstrated at least nominal significance with other metabolic traits in prior studies, and two loci exhibited coincident eQTLs (P < 1 × 10-5) in subcutaneous adipose tissue for BPTF and PDGFC. Taken together, these analyses identified multiple novel lipid loci, providing new potential therapeutic targets

The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

To dissect the genetic architecture of blood pressure and assess effects on target-organ damage, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry and genotypes from an additional 140,886 individuals were used for validation. We identified 66 blood pressure loci, of which 17 were novel and 15 harbored multiple distinct association signals. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in blood pressure control through modulation of vascular tone across multiple tissues. The 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent. The 66-SNP blood pressure risk score was significantly associated with target-organ damage in multiple tissues, with minor effects in the kidney. Our findings expand current knowledge of blood pressure pathways and highlight tissues beyond the classic renal system in blood pressure regulation

A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure

Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene-smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene-smoking interaction analysis and 38 were newly identified (P <5 x 10(-8), false discovery rate <0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.Peer reviewe

Balloon Mitral Commissurotomy for Mitral Stenosis After Resolution of a Large Mobile Left Atrial Thrombus by 2-year Warfarin Treatment

We report on a patient who was referred for percutaneous transvenous mitral commissurotomy for symptomatic mitral stenosis. However, transthoracic and transesophageal echocardiography both revealed a large mobile left atrial thrombus, occupying almost half of the left atrial body. Because the patient strongly declined surgical mitral treatment, he was administered warfarin for 2 years. Complete resolution of left atrial thrombus was confirmed by follow-up transesophageal echocardiography. Successful percutaneous transvenous mitral commissurotomy was undertaken without complications

A cluster of heritable pulmonary arterial hypertension cases in a family with all three siblings carrying the same novel AQP1 c.273C>G variant‐a case report

Abstract Approximately 25%–30% of patients diagnosed with idiopathic pulmonary arterial hypertension (PAH) have a clustered underlying Mendelian genetic cause and should be classified as heritable PAH (HPAH). The sixth World Symposium on Pulmonary Hypertension listed AQP1 as a PAH‐related gene. AQP1 and its protein product Aquaporin‐1 (AQP1) are found in abundance within pulmonary artery smooth muscle cells. Here, we report a family affected by HPAH with all three siblings carrying the same novel missense variant of AQP1 c.273C>G (p.Ile91Met). The youngest brother and the older sister both had dyspnea and edema and were diagnosed with HPAH about 10 years ago. In 2021, they received genetic tests that revealed all three siblings carried the same novel variant of AQP1 (c.273C>G). The brother in between these two siblings, although originally claimed to be asymptomatic, raised awareness. He then sought medical examination and confirmed the diagnosis of HPAH as well. This report on all three siblings carrying the same novel variant of AQP1 (c.273C>G) highlighted the importance of genetic testing and counseling for family members when PAH was first detected