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Lipoprotein(a) molar concentrations rather than genetic variants better predict coronary artery disease risk and

Jie Li1,2, Ben Ma1,2, Qin Fang1,2

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

Lipids in Health and Disease
|February 14, 2025
PubMed

Insights

Genetic variants in the LPA gene influence lipoprotein(a) [Lp(a)] levels in Chinese individuals. However, these variants do not reliably predict coronary artery disease (CAD) risk or severity.

Area of Science:

  • Cardiovascular Genetics
  • Molecular Epidemiology
  • Biochemistry

Background:

  • Elevated lipoprotein(a) [Lp(a)] is a known risk factor for coronary artery disease (CAD).
  • Lp(a) levels exhibit significant genetic determination and population variability.
  • Previous research on Lp(a) genetic variants has predominantly focused on Caucasian populations.

Purpose of the Study:

  • To investigate the association between LPA genetic variants, Lp(a) concentrations, and CAD in a Han Chinese cohort.
  • To evaluate the predictive value of LPA genetic variants for CAD incidence and severity.

Main Methods:

  • Recruitment of 3779 patients undergoing coronary angiography.
  • Quantification of LPA Kringle IV type 2 (KIV-2) copies using qPCR.
  • Genotyping of fifteen single nucleotide polymorphisms (SNPs) within the LPA gene.
  • Computation of an LPA genetic risk score (GRS) based on seven SNPs.
  • Statistical analysis using linear and logistic regression models.

Main Results:

  • Higher Lp(a) quartiles were significantly associated with increased odds of CAD, multivessel CAD, and high Gensini scores.
  • Both LPA GRS and KIV-2 quartiles demonstrated significant associations with Lp(a) concentrations.
  • After FDR correction, no significant associations were found between LPA genetic variants and CAD, multivessel CAD, or high Gensini scores.

Conclusions:

  • LPA genetic variants demonstrably influence Lp(a) levels in the Han Chinese population.
  • Lp(a) molar concentrations, rather than specific genetic variants, appear more critical for predicting CAD.
  • Emphasizes the clinical importance of Lp(a) detection and management for cardiovascular risk assessment.
Abstract

Keywords:
LPA geneEpidemiologyGenetic risk scoreGeneticsKringle IV type 2 copiesSingle nucleotide polymorphism

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