Research

14 pages, 2052 KiB

Open AccessArticle

Hepatic Transcriptomics Reveals Reduced Lipogenesis in High-Salt Diet Mice

by Jing Xu, Fei Mao, Yan Lu, Tiemin Liu, Xiaoying Li and Yao Li

Genes 2023, 14(5), 966; https://doi.org/10.3390/genes14050966 - 24 Apr 2023

Viewed by 1566

It has been demonstrated that a high salt diet (HSD) increases the risk of cardiovascular disease and metabolic dysfunction. In particular, the impact and molecular mechanisms of long-term HSD on hepatic metabolism remain largely unknown. To identify differentially expressed genes (DEGs) affecting the [...] Read more.

It has been demonstrated that a high salt diet (HSD) increases the risk of cardiovascular disease and metabolic dysfunction. In particular, the impact and molecular mechanisms of long-term HSD on hepatic metabolism remain largely unknown. To identify differentially expressed genes (DEGs) affecting the metabolism of liver tissues from HSD and control groups, a transcriptome analysis of liver tissues was performed in this study. As a result of the transcriptome analysis, the expression of genes related to lipid and steroid biosynthesis (such as Fasn, Scd1, and Cyp7a1) was significantly reduced in the livers of HSD mice. Additionally, several gene ontology (GO) terms have been identified as associated with metabolic processes in the liver, including the lipid metabolic process (GO: 0006629) and the steroid metabolic process (GO: 0008202). An additional quantitative RT-qPCR analysis was conducted to confirm six down-regulated genes and two up-regulated genes. Our findings provide a theoretical basis for further investigation of HSD-induced metabolic disorders. Full article

(This article belongs to the Special Issue Genetics of Cardiovascular Metabolism)

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16 pages, 2582 KiB

Open AccessArticle

Description of a Cohort with a New Truncating MYBPC3 Variant for Hypertrophic Cardiomyopathy in Northern Spain

by Natalia Fernández Suárez, María Teresa Viadero Ubierna, Jesús Garde Basas, María Esther Onecha de la Fuente, María Teresa Amigo Lanza, Gonzalo Martin Gorria, Adrián Rivas Pérez, Luis Ruiz Guerrero and Domingo González-Lamuño

Genes 2023, 14(4), 840; https://doi.org/10.3390/genes14040840 - 30 Mar 2023

Cited by 1 | Viewed by 1527

Abstract

Background: The pathogenicity of the different genetic variants causing hypertrophic cardiomyopathy (HCM) and the genotype/phenotype correlations are difficult to assess in clinical practice, as most mutations are unique or identified in non-informative families. Pathogenic variants in the sarcomeric gene MYBPC3 inherited with an [...] Read more.

Background: The pathogenicity of the different genetic variants causing hypertrophic cardiomyopathy (HCM) and the genotype/phenotype correlations are difficult to assess in clinical practice, as most mutations are unique or identified in non-informative families. Pathogenic variants in the sarcomeric gene MYBPC3 inherited with an autosomal dominant pattern, whereas incomplete and age-dependent penetrance are the most common causes of HCM. Methods: We describe the clinical characteristics of a new truncating MYBPC3 variant, p.Val931Glyfs*120, in 75 subjects from 18 different families from northern Spain with the p.Val931Glyfs*120 variant. Results: Our cohort allows us to estimate the penetrance and prognosis of this variant. The penetrance of the disease increases with age, whereas 50% of males in our sample developed HCM by the age of 36 years old, and 50% of women developed the disease by the time they reached 48 years of age (p = 0.104). Men have more documented arrhythmias with potential risk of sudden death (p = 0.018), requiring implantation of cardioverter defibrillators (p = 0.024). Semi-professional/competitive sport among males is related to earlier onset of HCM (p = 0.004). Conclusions: The p.Val931Glyfs*120 truncating variant in MYBPC3 is associated with a moderate phenotype of HCM, with a high penetrance, onset in middle age, and a worse outcome in males due to higher risk of sudden death due to arrhythmias. Full article

(This article belongs to the Special Issue Genetics of Cardiovascular Metabolism)

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19 pages, 1585 KiB

Open AccessArticle

Investigation of Genetic Causes in Patients with Congenital Heart Disease in Qatar: Findings from the Sidra Cardiac Registry

by Sarah Okashah, Dhanya Vasudeva, Aya El Jerbi, Houssein Khodjet-El-khil, Mashael Al-Shafai, Najeeb Syed, Marios Kambouris, Sharda Udassi, Luis R. Saraiva, Hesham Al-Saloos, Jai Udassi and Kholoud N. Al-Shafai

Genes 2022, 13(8), 1369; https://doi.org/10.3390/genes13081369 - 30 Jul 2022

Cited by 3 | Viewed by 2978

Abstract

Congenital heart disease (CHD) is one of the most common forms of birth defects worldwide, with a prevalence of 1–2% in newborns. CHD is a multifactorial disease partially caused by genetic defects, including chromosomal abnormalities and single gene mutations. Here, we describe the [...] Read more.

Congenital heart disease (CHD) is one of the most common forms of birth defects worldwide, with a prevalence of 1–2% in newborns. CHD is a multifactorial disease partially caused by genetic defects, including chromosomal abnormalities and single gene mutations. Here, we describe the Sidra Cardiac Registry, which includes 52 families and a total of 178 individuals, and investigate the genetic etiology of CHD in Qatar. We reviewed the results of genetic tests conducted in patients as part of their clinical evaluation, including chromosomal testing. We also performed whole exome sequencing (WES) to identify potential causative variants. Sixteen patients with CHD had chromosomal abnormalities that explained their complex CHD phenotype, including six patients with trisomy 21. Moreover, using exome analysis, we identified potential CHD variants in 24 patients, revealing 65 potential variants in 56 genes. Four variants were classified as pathogenic/likely pathogenic based on the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) classification; these variants were detected in four patients. This study sheds light on several potential genetic variants contributing to the development of CHD. Additional functional studies are needed to better understand the role of the identified variants in the pathogenesis of CHD. Full article

(This article belongs to the Special Issue Genetics of Cardiovascular Metabolism)

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18 pages, 2627 KiB

Open AccessArticle

Associations of Sex Steroids and Sex Hormone-Binding Globulin with Non-Alcoholic Fatty Liver Disease: A Population-Based Study and Meta-Analysis

by Xiaofang Zhang, Yuchan Mou, Elif Aribas, Masoud Amiri, Jana Nano, Wichor M. Bramer, Maryam Kavousi, Robert J. de Knegt, Eralda Asllanaj and Mohsen Ghanbari

Genes 2022, 13(6), 966; https://doi.org/10.3390/genes13060966 - 27 May 2022

Cited by 6 | Viewed by 2518

Abstract

Background: Prior studies have reported inconsistent results or less well-explored associations between sex hormones and non-alcoholic fatty liver disease (NAFLD). Here, we aimed to investigate the associations of NAFLD with sex steroids and sex hormone-binding globulin (SHBG) in the population-based study and conduct [...] Read more.

Background: Prior studies have reported inconsistent results or less well-explored associations between sex hormones and non-alcoholic fatty liver disease (NAFLD). Here, we aimed to investigate the associations of NAFLD with sex steroids and sex hormone-binding globulin (SHBG) in the population-based study and conduct a comprehensive systematic review and meta-analysis of all published observational studies. Methods: Analyses included 755 men and 1109 women with available data on sex steroids, SHBG, and ultrasound-based NAFLD from the Rotterdam Study. Multivariable regression models were used to examine the associations. Additionally, we searched five databases from inception to 1 April 2022 and performed a systematic review and meta-analysis. Random-effects (DerSimonian-Laird) method was used for meta-analysis, odds ratios (ORs) were calculated for the effect estimate, subgroup and leave-one-out sensitivity analyses were conducted, and meta-regression was performed to explore the pooled statistics with high heterogeneity. Results: In the Rotterdam Study, lower levels of SHBG were associated with NAFLD in both sexes, while lower testosterone was associated with NAFLD only among women. Similarly, the meta-analysis of 16 studies indicated no sex-specific association between SHBG and NAFLD (men: OR = 0.37, 95%CI 0.21–0.53; women: OR = 0.40, 95%CI 0.21–0.60), yet there was a sex-specific association between testosterone and NAFLD (men: OR = 0.59, 95%CI 0.42–0.76; women: OR = 1.06, 95%CI 0.68–1.44). Moreover, men with NAFLD had lower estradiol levels than those without NAFLD. Conclusions: Lower SHBG levels were associated with NAFLD in both sexes, but testosterone levels were associated in a sex-specific manner. In addition, our results showed estradiol with the potential as a protective factor for NAFLD in healthy men. Full article

(This article belongs to the Special Issue Genetics of Cardiovascular Metabolism)

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8 pages, 230 KiB

Open AccessArticle

Association of Myocardial Infarction with CDKN2B Antisense RNA 1 (CDKN2B-AS1) rs1333049 Polymorphism in Slovenian Subjects with Type 2 Diabetes Mellitus

by Miha Tibaut, Franjo Naji and Daniel Petrovič

Genes 2022, 13(3), 526; https://doi.org/10.3390/genes13030526 - 16 Mar 2022

Cited by 3 | Viewed by 1724

Abstract

Background: We examined the role of rs1333049 polymorphism of the CDKN2B Antisense RNA 1 (CDKN2B-AS1) on the prevalence of myocardial infarction (MI) in Slovenian subjects with type 2 diabetes mellitus (T2DM). Methods: A total of 1071 subjects with T2DM were enrolled in this [...] Read more.

Background: We examined the role of rs1333049 polymorphism of the CDKN2B Antisense RNA 1 (CDKN2B-AS1) on the prevalence of myocardial infarction (MI) in Slovenian subjects with type 2 diabetes mellitus (T2DM). Methods: A total of 1071 subjects with T2DM were enrolled in this retrospective cross-sectional case-control study. Of the subjects, 334 had a history of recent MI, and 737 subjects in the control group had no clinical signs of coronary artery disease (CAD). With logistic regression, we performed a genetic analysis of rs1333049 polymorphism in all subjects. Results: The C allele of rs1333049 polymorphism was statistically more frequent in MI subjects (p = 0.05). Subjects with CC genotype had a higher prevalence of MI than the control group in the co-dominant (AOR 1.50, CI 1.02–2.21, p = 0.04) and recessive (AOR 1.38, CI 1.09–1.89, p = 0.04) genetic model. Conclusions: According to our study, the C allele and CC genotype of rs1333049 polymorphism of CDKN2B-AS1 are possible markers of MI in T2DM subjects in the Slovenian population. Full article

(This article belongs to the Special Issue Genetics of Cardiovascular Metabolism)

16 pages, 2594 KiB

Open AccessArticle

Early Markers of Cardiovascular Disease Associated with Clinical Data and Autosomal Ancestry in Patients with Type 1 Diabetes: A Cross-Sectional Study in an Admixed Brazilian Population

by Roberta Maria Duailibe Ferreira Reis, Rossana Santiago de Sousa Azulay, Maria da Glória Tavares, Gilvan Cortês Nascimento, Sabrina da Silva Pereira Damianse, Viviane Chaves de Carvalho Rocha, Ana Gregória Almeida, Débora Cristina Ferreira Lago, Vandilson Rodrigues, Marcelo Magalhães, Carla Souza Sobral, Conceição Parente, Joana França, Jacqueline Ribeiro, Paulo Cézar Dias Ferraz, Carlos Alberto Azulay Junior, Dayse Aparecida Silva, Marília Brito Gomes and Manuel dos Santos Faria

Genes 2022, 13(2), 389; https://doi.org/10.3390/genes13020389 - 21 Feb 2022

Viewed by 1735

Abstract

Patients with type 1 diabetes (T1D) have a higher risk of developing cardiovascular disease (CVD), which is a major cause of death in this population. This study investigates early markers of CVD associated with clinical data and autosomal ancestry in T1D patients from [...] Read more.

Patients with type 1 diabetes (T1D) have a higher risk of developing cardiovascular disease (CVD), which is a major cause of death in this population. This study investigates early markers of CVD associated with clinical data and autosomal ancestry in T1D patients from an admixed Brazilian population. A cross-sectional study was conducted with 99 T1D patients. The mean age of the study sample was 27.6 years and the mean duration of T1D was 14.4 years. The frequencies of abnormalities of the early markers of CVD were 19.6% in the ankle-brachial index (ABI), 4.1% in the coronary artery calcium score (CACS), and 5% in the carotid Doppler. A significant percentage of agreement was observed for the comparison of the frequency of abnormalities between CACS and carotid Doppler (92.2%, p = 0.041). There was no significant association between the level of autosomal ancestry proportions and early markers of CVD. The ABI was useful in the early identification of CVD in asymptomatic young patients with T1D and with a short duration of disease. Although CACS and carotid Doppler are non-invasive tests, carotid Doppler is more cost-effective, and both have limitations in screening for CVD in young patients with a short duration of T1D. We did not find a statistically significant relationship between autosomal ancestry proportions and early CVD markers in an admixed Brazilian population. Full article

(This article belongs to the Special Issue Genetics of Cardiovascular Metabolism)

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13 pages, 971 KiB

Open AccessArticle

Circulatory MicroRNAs in Plasma and Atrial Fibrillation in the General Population: The Rotterdam Study

by Sven Geurts, Michelle M. J. Mens, Maxime M. Bos, M. Arfan Ikram, Mohsen Ghanbari and Maryam Kavousi

Genes 2022, 13(1), 11; https://doi.org/10.3390/genes13010011 - 22 Dec 2021

Cited by 10 | Viewed by 2648

Abstract

Background: MicroRNAs (miRNAs), small non-coding RNAs regulating gene expression, have been shown to play an important role in cardiovascular disease. However, limited population-based data regarding the relationship between circulatory miRNAs in plasma and atrial fibrillation (AF) exist. Moreover, it remains unclear if the [...] Read more.

Background: MicroRNAs (miRNAs), small non-coding RNAs regulating gene expression, have been shown to play an important role in cardiovascular disease. However, limited population-based data regarding the relationship between circulatory miRNAs in plasma and atrial fibrillation (AF) exist. Moreover, it remains unclear if the relationship differs by sex. We therefore aimed to determine the (sex-specific) association between plasma circulatory miRNAs and AF at the population level. Methods: Plasma levels of miRNAs were measured using a targeted next-generation sequencing method in 1999 participants from the population-based Rotterdam Study. Logistic regression and Cox proportional hazards models were used to assess the associations of 591 well-expressed miRNAs with the prevalence and incidence of AF. Models were adjusted for cardiovascular risk factors. We further examined the link between predicted target genes of the identified miRNAs. Results: The mean age was 71.7 years (57.1% women), 98 participants (58 men and 40 women) had prevalent AF at baseline. Moreover, 196 participants (96 men and 100 women) developed AF during a median follow-up of 9.0 years. After adjusting for multiple testing, miR-4798-3p was significantly associated with the odds of prevalent AF among men (odds ratio, 95% confidence interval, 0.39, 0.24–0.66, p-value = 0.000248). No miRNAs were significantly associated with incident AF. MiR-4798-3p could potentially regulate the expression of a number of AF-related genes, including genes involved in calcium and potassium handling in myocytes, protection of cells against oxidative stress, and cardiac fibrosis. Conclusions: Plasma levels of miR-4798-3p were significantly associated with the odds of prevalent AF among men. Several target genes in relation to AF pathophysiology could potentially be regulated by miR-4798-3p that warrant further investigations in future experimental studies. Full article

(This article belongs to the Special Issue Genetics of Cardiovascular Metabolism)

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14 pages, 1985 KiB

Open AccessArticle

A Genome-Wide Association Study of a Korean Population Identifies Genetic Susceptibility to Hypertension Based on Sex-Specific Differences

by Seong-Beom Cho and Jinhwa Jang

Genes 2021, 12(11), 1804; https://doi.org/10.3390/genes12111804 - 16 Nov 2021

Cited by 2 | Viewed by 2261

Abstract

Genome-wide association studies have expanded our understanding of the genetic variation of hypertension. Hypertension and blood pressure are influenced by sex-specific differences; therefore, genetic variants may have sex-specific effects on phenotype. To identify the genetic factors influencing the sex-specific differences concerning hypertension, we [...] Read more.

Genome-wide association studies have expanded our understanding of the genetic variation of hypertension. Hypertension and blood pressure are influenced by sex-specific differences; therefore, genetic variants may have sex-specific effects on phenotype. To identify the genetic factors influencing the sex-specific differences concerning hypertension, we conducted a heterogeneity analysis of a genome-wide association study (GWAS) on 13,926 samples from a Korean population. Using the Illumina exome chip data of the population, we performed GWASs of the male and female population independently and applied a statistical test that identified heterogeneous effects of the variants between the two groups. To gain information about the biological implication of the genetic heterogeneity, we used gene set enrichment analysis with GWAS catalog and pathway gene sets. The heterogeneity analysis revealed that the rs11066015 of ACAD10 was a significant locus that had sex-specific genetic effects on the development of hypertension. The rs2074356 of HECTD4 also showed significant genetic heterogeneity in systolic blood pressure. The enrichment analysis showed significant results that are consistent with the pathophysiology of hypertension. These results indicate a sex-specific genetic susceptibility to hypertension that should be considered in future genetic studies of hypertension. Full article

(This article belongs to the Special Issue Genetics of Cardiovascular Metabolism)

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Review

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12 pages, 411 KiB

Open AccessFeature PaperReview

Integrative Genetic Approach Facilitates Precision Strategies for Acute Myocardial Infarction

by Muzamil Khawaja, Rehma Siddiqui, Salim S. Virani, Christopher I. Amos, Dhrubajyoti Bandyopadhyay, Hafeez Ul Hassan Virk, Mahboob Alam, Hani Jneid and Chayakrit Krittanawong

Genes 2023, 14(7), 1340; https://doi.org/10.3390/genes14071340 - 26 Jun 2023

Viewed by 1312

Abstract

Acute myocardial infarction remains a significant cause of mortality worldwide and its burden continues to grow. Its pathophysiology is known to be complex and multifactorial, with several acquired and inherited risk factors. As advances in technology and medical therapy continue, there is now [...] Read more.

Acute myocardial infarction remains a significant cause of mortality worldwide and its burden continues to grow. Its pathophysiology is known to be complex and multifactorial, with several acquired and inherited risk factors. As advances in technology and medical therapy continue, there is now increasing recognition of the role that genetics play in the development and management of myocardial infarction. The genetic determinants of acute coronary syndrome are still vastly understudied, but the advent of whole-genome scanning and genome-wide association studies has significantly expanded the current understanding of genetics and simultaneously fostered hope that genetic profiling and gene-guided treatments could substantially impact clinical outcomes. The identification of genes associated with acute myocardial infarction can help in the development of personalized medicine, risk stratification, and improved therapeutic strategies. In this context, several genes have been studied, and their potential involvement in increasing the risk for acute myocardial infarction is being investigated. As such, this article provides a review of some of the genes potentially related to an increased risk for acute myocardial infarction as well as the latest updates in gene-guided risk stratification and treatment strategies. Full article

(This article belongs to the Special Issue Genetics of Cardiovascular Metabolism)

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14 pages, 1532 KiB

Open AccessReview

Potential Involvement of LncRNAs in Cardiometabolic Diseases

by Mirolyuba Ilieva and Shizuka Uchida

Genes 2023, 14(1), 213; https://doi.org/10.3390/genes14010213 - 13 Jan 2023

Cited by 1 | Viewed by 1905

Abstract

Characterized by cardiovascular disease and diabetes, cardiometabolic diseases are a major cause of mortality around the world. As such, there is an urgent need to understand the pathogenesis of cardiometabolic diseases. Increasing evidence suggests that most of the mammalian genome are transcribed as [...] Read more.

Characterized by cardiovascular disease and diabetes, cardiometabolic diseases are a major cause of mortality around the world. As such, there is an urgent need to understand the pathogenesis of cardiometabolic diseases. Increasing evidence suggests that most of the mammalian genome are transcribed as RNA, but only a few percent of them encode for proteins. All of the RNAs that do not encode for proteins are collectively called non-protein-coding RNAs (ncRNAs). Among these ncRNAs, long ncRNAs (lncRNAs) are considered as missing keys to understand the pathogeneses of various diseases, including cardiometabolic diseases. Given the increased interest in lncRNAs, in this study, we will summarize the latest trend in the lncRNA research from the perspective of cardiometabolism and disease by focusing on the major risk factors of cardiometabolic diseases: obesity, cholesterol, diabetes, and hypertension. Because genetic inheritance is unavoidable in cardiometabolic diseases, we paid special attention to the genetic factors of lncRNAs that may influence cardiometabolic diseases. Full article

(This article belongs to the Special Issue Genetics of Cardiovascular Metabolism)

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8 pages, 1614 KiB

Open AccessCase Report

AKAP9-Related Channelopathy: Novel Pathogenic Variant and Review of the Literature

by Minh-Tuan Huynh, Alexis Proust, Jérôme Bouligand and Elena Popescu

Genes 2022, 13(11), 2167; https://doi.org/10.3390/genes13112167 - 20 Nov 2022

Cited by 3 | Viewed by 1832

Abstract

Disease-associated pathogenic variants in the A-Kinase Anchor Protein 9 (AKAP9) (MIM *604001) have been recently identified in patients with autosomal dominant long QT syndrome 11 (MIM #611820), lethal arrhythmia (ventricular fibrillation, polymorphic ventricular tachycardia), Brugada syndrome, and sudden unexpected death. However, [...] Read more.

Disease-associated pathogenic variants in the A-Kinase Anchor Protein 9 (AKAP9) (MIM *604001) have been recently identified in patients with autosomal dominant long QT syndrome 11 (MIM #611820), lethal arrhythmia (ventricular fibrillation, polymorphic ventricular tachycardia), Brugada syndrome, and sudden unexpected death. However, AKAP9 sequence variations were rarely reported and AKAP9 was classified as a “disputed evidence” gene to support disease causation due to the insufficient genetic evidence and a limited number of reported AKAP9-mutated patients. Here, we describe a 47-year-old male carrying a novel frameshift AKAP9 pathogenic variant who presented recurrent syncopal attacks and sudden cardiac arrest that required a semi-automatic external defibrillator implant and an electric shock treatment of ventricular arrhythmia. This study provides insight into the mechanism underlying cardiac arrest and confirms that AKAP9 loss-of-function variants predispose to serious, life-threatening ventricular arrhythmias. Full article

(This article belongs to the Special Issue Genetics of Cardiovascular Metabolism)

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