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Distinct genetic architecture of coronary heart disease in dyslipidemia patients

Man Huang1,2, Xiuli Song1,2, Shuni Zhou3

  • 1Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095# Jiefang Ave, Wuhan, 430030, PR China.

BMC Medical Genomics
|May 13, 2026
PubMed

Insights

This study identifies novel genes linked to dyslipidemia and coronary heart disease (CHD) in the Chinese Han population. Findings suggest extracellular matrix remodeling plays a role in atherosclerotic progression, offering new insights into CHD development.

Area of Science:

  • Genetics
  • Cardiovascular Disease
  • Metabolic Disorders

Background:

  • Established mutations in LDLR, APOB, and PCSK9 cause hypercholesterolemia, while LPL mutations are linked to hypertriglyceridemia.
  • These known mutations do not fully explain all dyslipidemia cases or the varying risk of coronary heart disease (CHD) among affected individuals.

Purpose of the Study:

  • To investigate the genetic landscape of dyslipidemia in the Chinese Han population.
  • To identify novel genes associated with hypercholesterolemia and hypertriglyceridemia beyond canonical lipid pathways.
  • To explore genetic differences between patients with and without CHD within the hypercholesterolemia cohort.

Main Methods:

  • Whole exome sequencing (WES) was performed on 108 patients with lipid disturbances and 414 controls.
  • Candidate genes were assessed using the optimal sequence kernel association test (SKAT-O).
  • Subgroup analysis compared genetic profiles between CHD and non-CHD patients in the hypercholesterolemia cohort.

Main Results:

  • Pathogenic variants were identified in LDLR, LPL, and APOA5.
  • SKAT-O identified 192 and 184 additional genes associated with hypercholesterolemia and hypertriglyceridemia, respectively, after excluding known pathogenic variants.
  • 119 genes were found relevant to CHD, with COL5A1, COL24A1, COL6A6, COL6A2, SLC3A1, ATP1A4, and SLC7A9 identified as candidate causal genes.

Conclusions:

  • This study reveals a broader genetic spectrum of dyslipidemia in the Chinese Han population, including novel susceptibility genes.
  • Genes implicated in CHD suggest extracellular matrix remodeling as a potential mediator of atherosclerotic progression in hypercholesterolemia.
  • The findings offer new mechanistic insights into CHD development and identify potential targets for future functional studies.
Abstract

Keywords:
APOBLDLRPCSK9Coronary heart diseaseHypercholesterolemiaHypertriglyceridemiaLPL and extracellular matrixWhole exome sequencing

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