ATP10D – Myocardial Infarction

ATP10D has been robustly associated with myocardial infarction in recent genetic studies. Large-scale genome‑wide association studies in European populations have identified ATP10D as one of the key genes in sphingolipid metabolism whose variants correlate with myocardial infarction risk (PMID:19798445). The analysis encompassed 32 significantly associated variants across diverse lipid traits, and among these, ATP10D showed consistent associations with cardiovascular indices. These findings have been reproduced in independent cohorts, including a Japanese study focusing on atherosclerotic indices where the ATP10D locus (via variant rs2351791) was also linked to myocardial infarction (PMID:24125428).

The genetic evidence derives from rigorous statistical analyses in large cohorts, lending a high level of confidence to the association. While exact proband or family counts are not provided due to the population‐based nature of GWAS, the replication across multiple ethnic groups and independent studies supports a strong gene–disease link. The studies employed comprehensive SNP arrays and correction for multiple comparisons, which reinforces the validity of the reported associations. Such genomic approaches are particularly useful in dissecting the polygenic architecture of complex traits like myocardial infarction.

In terms of genetic evidence, the studies did not rely on traditional familial segregation but instead capitalized on large sample sizes and multi‐ethnic replication to establish statistical significance. Although a valid HGVS‐formatted coding variant was not explicitly provided in the reported data, the association of ATP10D with myocardial infarction is supported by the aggregate signal from multiple SNPs within the gene region. This type of evidence is increasingly influential in complex disease genetics where single variants may contribute modest effects. Therefore, the genetic evidence is tiered as strong despite the lack of a single definitive variant description.

Functional data directly connecting ATP10D to myocardial infarction remain limited. However, ATP10D is implicated in phospholipid translocation in cellular membranes, a function that plausibly influences lipid metabolism and thereby cardiovascular risk. No detailed functional assays or animal models were provided to further elaborate on the molecular mechanism. This gap in experimental evidence limits the functional scoring despite strong genetic associations. Future studies are required to delineate the mechanistic pathways by which ATP10D variants influence myocardial infarction risk.

No significant conflicting evidence has been reported in the available literature; both European and Japanese studies underscore a similar association with myocardial infarction. The convergence of robust GWAS findings and the biological plausibility based on ATP10D’s role in lipid homeostasis provides a coherent narrative supporting the gene–disease relationship. It is notable that while additional genetic signals exist from the broader sphingolipid pathway, the association with ATP10D consistently emerges as significant across studies.

In summary, multiple independent studies provide strong genetic evidence linking ATP10D with myocardial infarction. Although direct functional studies are currently limited, the gene’s role in lipid regulation offers a credible pathogenic mechanism. Key take‑home: ATP10D variants contribute significantly to myocardial infarction susceptibility and warrant further investigation for potential diagnostic and therapeutic applications.

References

• PLoS Genetics • 2009 • Genetic determinants of circulating sphingolipid concentrations in European populations PMID:19798445
• Atherosclerosis • 2013 • A gene variant in the Atp10d gene associates with atherosclerotic indices in Japanese elderly population PMID:24125428

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