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Exploring LDLR-APOB Interactions in Familial Hypercholesterolemia in the Vietnamese Population: A Protein-Protein

Ngoc-Thanh Kim1,2, Doan-Loi Do1,2, Mai-Ngoc Thi Nguyen2

  • 1Department of Cardiology, Hanoi Medical University, Hanoi, Vietnam.

Bioinformatics and Biology Insights
|December 2, 2024
PubMed

Insights

This study identifies novel mutations in LDLR and APOB genes in the Vietnamese population, revealing detrimental protein interactions linked to atherosclerotic cardiovascular diseases (CVDs) and familial hypercholesterolemia (FH).

Area of Science:

  • Genetics and Molecular Biology
  • Cardiovascular Research
  • Bioinformatics

Background:

  • Atherosclerotic cardiovascular diseases (CVDs) are significantly influenced by genetic factors, including mutations in low-density lipoprotein receptor (LDLR) and apolipoprotein B (APOB) genes, which are common causes of familial hypercholesterolemia (FH).
  • Understanding the specific genetic variations and their molecular impact within diverse populations, such as the Vietnamese population, is crucial for accurate diagnosis and targeted therapies.

Purpose of the Study:

  • To identify novel LDLR and APOB mutations in the Vietnamese population and elucidate their implications in cardiovascular disease (CVD) development.
  • To investigate the structural and functional consequences of these mutations on protein-protein interactions using computational modeling and molecular docking.

Main Methods:

  • Comprehensive bioinformatic analysis to detect novel LDLR and APOB mutations.
  • Homology modeling to predict the 3D structures of wild-type and mutant proteins.
  • Protein-protein molecular docking to assess the impact of mutations on binding affinities between LDLR and APOB.

Main Results:

  • Identification of 10 novel binding residues in LDLR, including ASP-47, GLY-48, and GLU-51.
  • Analysis of 154 protein complexes revealed 5 specific mutant isoforms (APOB-LDLR) exhibiting low binding affinities and significant hydrogen-bonding interactions.
  • Detected potentially detrimental interactions, such as APOB (Arg3527Trp)-LDLR (Cys318Arg) and APOB (His3583Leu)-LDLR (Cys104Tyr).

Conclusions:

  • The identified novel mutations and their resulting protein interactions provide insights into the molecular mechanisms underlying CVD and FH.
  • These findings highlight potential therapeutic targets for managing atherosclerotic cardiovascular diseases.
  • The study enhances the understanding of genetic variations in FH and can guide future research in this area.

Keywords:
APOBLDLRfamilial hypercholesterolemiahomology modelinginteraction

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