Genetic variants linked to inherited cardiomyopathies; disease penetrance remains low
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Cardiomyopathy and HF diagnosis were more common among individuals with certain pathogenic variants compared with those without; however, prevalence was low, between 1% and 3% overall, researchers reported.
The results of a large study evaluating the overall prevalence and expression of pathogenic variants associated with inherited cardiomyopathies in participants from the UK Biobank were published in Circulation: Genomic and Precision Medicine.
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Pathogenic variants
“In this study, we leveraged the largest European population database, including whole exome sequencing and phenotype data, to evaluate the prevalence and penetrance of previously reported pathogenic and likely pathogenic variants associated with arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy and hypertrophic cardiomyopathy,” Mimount Bourfiss, MD, of the division of cardiology at University Medical Center Utrecht in the Netherlands, and colleagues wrote.
Utilizing the UK Biobank database, Bourfiss and colleagues identified pathogenic and likely pathogenic variants associated with arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy and hypertrophic cardiomyopathy (HCM) among 200,643 individuals who underwent whole-exome sequencing.
Within this large cohort, the prevalence of variants previously associated with the three conditions were as follows:
- arrhythmogenic right ventricular cardiomyopathy in one in 578 individuals;
- dilated cardiomyopathy in one in 251 individuals; and
- HCM in one in 149 individuals.
CV risk factors were similar between patients with and without cardiomyopathy-related genetic variants; however, those with HCM variants more often had diabetes (11.4% vs. 9.2%; P = .008) and those with dilated cardiomyopathy variants were more often smokers (46.4% vs. 41.4%; P = .007) compared with individuals without either genetic variant.
Among individuals who carried a genetic variant, 1.2% of those with an arrhythmogenic right ventricular cardiomyopathy variant, 3.1% of those with a dilated cardiomyopathy variant and 2.6% of those with a HCM variant were subsequently diagnosed with HF or a cardiomyopathy without previous chronic ischemic heart disease, according to the study.
Among individuals with an undiagnosed variant, 3.2% of those with an arrhythmogenic right ventricular cardiomyopathy variant, 1.8% of those with a dilated cardiomyopathy variant and 0.5% of those with a HCM variant had ventricular arrhythmias or abnormal finding on cardiac MRI.
Outcomes data
Compared with participants with no pathogenic variants, those with dilated cardiomyopathy variants had a higher rate of CV mortality (OR = 1.67; 95% CI, 1.04-2.59; P = .03), but the same was not true for those with an arrhythmogenic right ventricular cardiomyopathy variant or an HCM variant (P for both > .1), according to the researchers.
Diagnosis of HF or cardiomyopathy was more common in participants with dilated cardiomyopathy variants (OR = 3.66; 95% CI, 2.24-5.81; P = 4.9 x 10-7) and in those with HCM variants (OR = 3.03; 95% CI, 1.98-4.56; P = 5.8 x 10-7), but not in those with arrhythmogenic right ventricular cardiomyopathy variants (P = .172), compared with those with no variants, Bourfiss and colleagues wrote.
“Genetic screening and cardiological examination are necessary in family members of genetic cardiomyopathy patients since disease expression in family members is considerable,” the researchers wrote. “Disease expression in the general population, on the other hand, is low. Therefore, in case of an incidental finding, multiple factors like family history, presence of symptoms, electrical and/or structural abnormalities and gene and variant type should inform follow-up decisions. Further studies on the genotype-phenotype associations and disease penetrance will aid in facilitating these decisions.”
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