Related Experiment Video

Updated: Jun 28, 2026

Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model
03:45

Investigating the Pathogenesis of MYH7 Mutation Gly823Glu in Familial Hypertrophic Cardiomyopathy using a Mouse Model

Published on: August 8, 2022

Genetically predicted lower FLT3L levels increase the risk of hypertrophic cardiomyopathy partly mediated by

Yanhui Li1, Rumeng Chen2, Chunyan Hou2

  • 1Hunan Key Laboratory of the Research and Development of Novel Pharmaceutical Preparations, School of Pharmaceutical Science, Changsha Medical University, Changsha, China.

Medicine
|June 27, 2026
PubMed

Insights

Higher phosphate levels increase hypertrophic cardiomyopathy risk. Fms-related tyrosine kinase 3 ligand (FLT3L) shows an inverse association with HCM risk, potentially mediated by phosphate.

Area of Science:

  • Cardiovascular Genetics
  • Metabolic Disease Research
  • Inflammation and Immunity

Background:

  • Hypertrophic cardiomyopathy (HCM) is a complex cardiac condition with genetic and environmental influences.
  • Phosphate homeostasis and inflammatory markers like Fms-related tyrosine kinase 3 ligand (FLT3L) are implicated in cardiovascular health.
  • Understanding the interplay between these factors is crucial for identifying novel therapeutic targets.

Purpose of the Study:

  • To investigate the causal associations of FLT3L and phosphate levels with the risk of HCM using a Mendelian randomization approach.
  • To explore the potential mediating role of phosphate levels in the relationship between FLT3L and HCM.
  • To elucidate the genetic underpinnings of HCM risk related to inflammation and mineral metabolism.

Main Methods:

  • A two-step Mendelian randomization (MR) study design was employed.
  • Genetic variants for FLT3L and 75 inflammatory factors were identified from large-scale genome-wide association studies (GWAS).
  • Summary statistics for circulating phosphate and HCM were obtained from UK Biobank and FinnGen, respectively, with inverse-variance weighted methods used for primary analysis.

Main Results:

  • Genetically predicted higher phosphate levels were significantly associated with an increased risk of HCM (OR = 1.36, P = 4.82 × 10⁻²).
  • FLT3L demonstrated an inverse association with HCM risk (OR = 0.79, P = 4.10 × 10⁻²), and also with phosphate levels (β = -0.05, P = 1.70 × 10⁻⁹).
  • Mediation analysis indicated that phosphate levels partially mediated the effect of FLT3L on HCM risk, accounting for 12.05% of the total effect.

Conclusions:

  • Genetic liability to lower FLT3L levels is associated with a higher risk of developing HCM.
  • Circulating phosphate levels may act as a partial mediator in the pathway linking FLT3L to HCM risk.
  • These findings highlight the complex interplay between inflammation, mineral metabolism, and hypertrophic cardiomyopathy, suggesting potential avenues for future research and intervention.
Keywords:
2-step Mendelian randomizationFLT3Lcausal mediation analysishypertrophic cardiomyopathyphosphate metabolism

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