Hypertrophic Cardiomyopathy: The Impact of ALPK3 Gene Mutations

Hypertrophic cardiomyopathy (HCM) is a prevalent heart condition in South Korea, affecting about 1 in 300 people. This disease involves the thickening of the heart muscle, which can lead to heart failure and sudden cardiac death. Traditionally, mutations in sarcomere protein genes like MYBPC3 and MYH7 are linked to HCM. However, the ALPK3 gene, typically associated with severe childhood autosomal recessive HCM, has recently been implicated in adult-onset autosomal dominant HCM due to monoallelic premature termination variants (PTVs). Most studies on ALPK3 PTVs have involved European populations. However, ALPK3 heterozygous was forth most common gene is korean HCMP population. 

This study investigates whether these variants also significantly affect Korean individuals.

Study Overview by Research and Development Center, 3billion, Inc.

The study done by “Research and Development Center, 3billion, Inc., Seoul, Republic of Korea” analyzed 2,366 Korean patients with nonsyndromic HCM who underwent Exome sequencing from 2019 to 2023.

Key Findings

The study identified 36 unrelated HCM patients (1.5%) with rare pathogenic or likely pathogenic PTVs in ALPK3. The median age of these patients was 52 years. The prevalence of ALPK3 PTVs was significantly higher in the Korean HCM cohort, with an odds ratio of 15.33, compared to control populations. This odds ratio is consistent with the 16.11 reported in previous European studies, indicating a similar risk factor across different ethnicities.

Implications of the Findings

These findings suggest that monoallelic ALPK3 PTV carriers have an elevated risk of developing adult-onset HCM, regardless of ethnicity. This emphasizes the importance of including ALPK3 PTVs in genetic screenings and diagnostic protocols for nonsyndromic HCM. Early identification of individuals at risk can facilitate timely interventions and improved management of the condition.

Conclusion

The significant enrichment of ALPK3 PTVs in Korean HCM patients underscores the gene’s critical role in the disease’s pathogenesis. The data from 3billion’s large Korean cohort provides valuable insights into HCM’s genetic landscape in East Asian populations, paving the way for more targeted therapeutic and preventive strategies. The results highlight the need for genetic diversity in research to fully understand the global impact of specific genetic variants on diseases like HCM.

At 3billion, we recognize the transformative power of genetic data analysis in uncovering new genetic diagnoses. We envision a future where our cutting-edge techniques lead to more precise treatments and preventive measures.

You can read the publication here: High prevalence of ALPK3 premature terminating variants in Korean hypertrophic cardiomyopathy patients