Genetic Variants Associated with Supernormal Coronary Arteries

Abstract

Aims: Genetic and medical insights from studies on cardioprotective phenotypes aid the development of novel therapeutics. This study identified genetic variants associated with supernormal coronary arteries using genomewide association study data and the corresponding genes based on expression quantitative trait loci (eQTL).Methods: Study participants were selected from two Korean cohorts according to inclusion criteria that included males with high cardiovascular risk (Framingham risk score ≥ 14, 10-year risk ≥ 16%) but with normal coronary arteries (supernormal group) or coronary artery disease (control group). After screening 12,309 individuals, males meeting the supernormal phenotype (n=72) and age-matched controls (n=94) were enrolled. Genetic variants associated with the supernormal phenotype were identified using Firth's logistic regression, and eQTL was used to evaluate whether the identified variants influence the expression of particular genes in human tissues.Results: Approximately 5 million autosomal variants were tested for association with the supernormal phenotype, and 10 independent loci suggestive of supernormal coronary arteries (p＜5.0×10 −5 ) were identified. The lead variants were seven intergenic single-nucleotide polymorphisms (SNPs), including one near PBX1, and three intronic SNPs, including one in PPFIA4. Of these variants or their proxies, rs9630089, rs6427989, and rs4984694 were associated with expression levels of SLIT1 and ARHGAP19, PPFIA4, and METTL26 in human tissues, respectively. These eQTL results supported their potential biological relevance.Conclusions: This study identified genetic variants and eQTL genes associated with supernormal coronary arteries. These results suggest candidate genes representing potential therapeutic targets for coronary artery disease.

Identification and validation of potential hypoxia-related genes associated with coronary artery disease

“…PTPRF Interacting Protein Alpha 4 (PPFIA4), which belongs to the PPFIA family, possesses different physiological functions in humans. A previous study discovered that variants of PPFIA4 were associated with supernormal coronary arteries and atrial fibrillation ( Low et al, 2017 ; Kim et al, 2022 ). FAM162A may serve as possible therapeutic and diagnostic targets for human dilated and ischemic cardiomyopathies because it was differentially expressed at the transcriptomic and proteomic levels in a number of rodent and human heart disease models ( Lee et al, 2020 ).…”

Clinical and Genetic Analysis of A Father-Son Duo with Monomelic Amyotrophy: Case Report

“…[ 24 ] Thus, it is plausible that mutations in SLIT1 and RYR3 may contribute to pathogenesis of MMA and hence need to be evaluated in a larger subset of patients. It is important to mention that mutations in SLIT1 have been reported in patients affected with neuroblastoma, acquired aplastic anaemia, supernormal coronary arteries and attention-deficit hyperactivity disorder,[ 25 , 26 , 27 , 28 ] and mutations in RYR3 have been implicated in nemaline myopathy, Alzheimer's disease, gender dysphoria and autism spectrum disorders. [ 24 , 29 , 30 , 31 ] Another identified deleterious variant worth mentioning is ARPP21, which has been shown to be associated with ALS in Europe and the United Kingdom,[ 32 , 33 , 34 ] but did not appear to be a risk factor in patients from Australia and mainland China[ 35 , 36 ] and hence may be investigated in MMA as well as ALS patients from different ethnic groups.…”

Lipid-lowering and kidney

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Genetic analysis [1,2], particularly the Mendelian randomization approach, has become one of the most important studying tools for contemporary life science, including lipidology and pharmacology. In the current issue, Park et al [3] demonstrated that genetically predicted HMGCR inhibition is associated with a low estimated glomerular filtration rate (eGFR), while that of PCSK9 is associated with high eGFR using a Mendelian randomization study.

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