CETP and LCAT Gene Polymorphisms Are Associated with High-Density Lipoprotein Subclasses and Acute Coronary Syndrome
Gilberto Vargas-Alarcon1,2, Oscar Perez-Mendez1,2, Gabriel Herrera-Maya1
1Department of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, 14080, Mexico City, Mexico.
Insights
Genetic variations in CETP (rs708272) and LCAT (rs2292318) are linked to acute coronary syndrome (ACS) risk and altered high-density lipoprotein cholesterol (HDL-C) levels and subclasses. These findings highlight genetic factors influencing cardiovascular health.
Area of Science:
- Cardiovascular Genetics
- Lipid Metabolism
- Molecular Epidemiology
Background:
- Genetic polymorphisms in cholesteryl ester transfer protein (CETP) and lecithin-cholesterol acyltransferase (LCAT) may influence lipid profiles and cardiovascular disease risk.
- High-density lipoprotein (HDL) size and subclass cholesterol levels are critical determinants of cardiovascular health.
- Understanding the genetic underpinnings of HDL metabolism is crucial for assessing acute coronary syndrome (ACS) susceptibility.
Purpose of the Study:
- To investigate the association between CETP and LCAT gene polymorphisms and ACS susceptibility.
- To examine the impact of these polymorphisms on HDL size distribution and cholesterol levels within HDL subclasses.
- To identify specific genetic variants that may contribute to the development of coronary atherosclerosis.
Main Methods:
- Genotyping of CETP (rs4783961, rs708272) and LCAT (rs2292318) polymorphisms using 5' exonuclease TaqMan assays in 619 ACS patients and 607 controls.
- Analysis of HDL subclasses and their cholesterol content in 100 healthy individuals using ultracentrifugation and native polyacrylamide gradient gel electrophoresis.
- Statistical analysis including dominant models and linkage disequilibrium to assess associations with ACS risk and HDL parameters.
Main Results:
- The G allele of CETP rs708272 polymorphism was significantly associated with an increased risk of ACS (OR = 1.45, pCDom = 0.036).
- Linkage disequilibrium analysis identified a combination of polymorphisms associated with increased ACS risk (OR = 1.52, pC = 0.02).
- CETP rs708272 G allele carriers exhibited lower cholesterol in HDL2a and HDL3a subclasses.
- LCAT rs2292318 A allele carriers showed reduced overall HDL cholesterol (HDL-C) and cholesterol in all five HDL subclasses.
Conclusions:
- The CETP rs708272 polymorphism is a significant risk factor for developing ACS.
- Both CETP rs708272 and LCAT rs2292318 polymorphisms are associated with altered HDL-C levels and HDL subclass cholesterol content.
- These genetic variations may play a role in the pathogenesis of coronary atherosclerosis and influence lipid metabolism.
Abstract:
We evaluated whether CETP and LCAT gene polymorphisms are statistically associated with the high-density lipoprotein (HDL) size distribution, the cholesterol level of HDL subclasses, and the acute coronary syndrome (ACS) susceptibility. Two CETP gene polymorphisms (rs4783961 and rs708272) and one LCAT polymorphism (rs2292318) were genotyped by 5' exonuclease TaqMan assays in 619 patients with ACS and 607 control individuals. For HDL analysis, a subgroup of 100 healthy individuals was recruited; the HDL subclasses were separated via ultracentrifugation and polyacrylamide gradient gel electrophoresis under native conditions. Under a dominant model, the G allele of the rs708272 polymorphism was associated with an increased risk of ACS (odds ratios [OR] = 1.45, corrected p-value [pCDom ] = 0.036). The linkage disequilibrium analysis showed that one of the eight possible combinations was associated with the risk of developing ACS (OR = 1.52, pC = 0.02), which suggests that it may contribute to coronary atherosclerosis. The rs708272 G allele carriers had a lower concentration of cholesterol associated with the HDL2a and HDL3a subclasses when compared with subjects carrying the A allele. Carriers of LCAT rs2292318 A allele showed a lower concentration of high-density lipoprotein-cholesterol (HDL-C) in comparison to the GG genotype; the cholesterol associated with the each one of the five HDL subclasses was significantly lower in rs2292318 A than in GG subjects. In summary, this study demonstrates that the rs708272 polymorphism is associated with a heightened risk of developing ACS. In addition, we report the association of the rs708272 and rs2292318 polymorphisms with HDL-C levels and HDL subclasses.
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