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Polymorphisms at LDLR locus may be associated with coronary artery disease through modulation of coagulation factor

Nicola Martinelli1, Domenico Girelli, Barbara Lunghi

  • 1Department of Medicine, University of Verona, Verona, Italy. nicola.martinelli@univr.it

Blood
|September 3, 2010
PubMed

Insights

Genetic variations in the Low-Density Lipoprotein Receptor (LDLR) gene influence coagulation factor VIII (FVIII) levels. Certain LDLR gene polymorphisms are linked to coronary artery disease (CAD) risk, independent of cholesterol levels.

Area of Science:

  • Genetics
  • Cardiovascular Medicine
  • Biochemistry

Background:

  • Elevated coagulation factor VIII (FVIII) levels are linked to cardiovascular disease (CVD).
  • The Low-Density Lipoprotein Receptor (LDLR) plays a role in clearing FVIII from plasma.
  • Understanding genetic factors influencing FVIII and CVD risk is crucial.

Purpose of the Study:

  • To investigate the association between single nucleotide polymorphisms (SNPs) in the SMARCA4-LDLR gene locus and FVIII coagulant activity (FVIII:c).
  • To determine if these SNPs are associated with coronary artery disease (CAD) risk.
  • To explore the relationship between LDLR gene variants, FVIII:c, and plasma lipid levels in relation to CAD.

Main Methods:

  • Genotyping of three SNPs (rs1122608, rs2228671, rs688) in the SMARCA4-LDLR locus.
  • Measurement of FVIII:c in subjects with and without angiographically confirmed CAD.
  • Statistical analysis including logistic regression and haplotype analysis, adjusting for cardiovascular risk factors.

Main Results:

  • High FVIII:c was an independent risk factor for CAD.
  • SNPs rs688 and rs2228671 predicted FVIII:c, with T alleles linked to higher levels.
  • The rs688 T allele was associated with increased CAD risk, while rs1122608 T allele was linked to decreased CAD prevalence.
  • rs688 remained a significant predictor of CAD after adjusting for lipids.

Conclusions:

  • Polymorphisms in the LDLR gene locus influence FVIII:c levels.
  • Specific LDLR gene variants are associated with CAD risk, potentially independent of plasma lipid concentrations.
  • These findings highlight a genetic link between FVIII regulation, LDLR function, and cardiovascular health.

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