ORIGINAL ARTICLE CETP and LCAT Gene Polymorphisms Are Associated with High-Density Lipoprotein Subclasses and Acute Coronary Syndrome Gilberto Vargas-Alarcon 1,2 · Oscar Perez-Mendez 1,2 · Gabriel Herrera-Maya 1 · Cynthia Garcia-Sanchez 1 · Marco Antonio Martinez-Rios 3 · Marco Antonio Peña-Duque 3 · Rosalinda Posadas-Sanchez 4 · Carlos Posadas-Romero 4 · Galileo Escobedo 5 · Jose Manuel Fragoso 1,2 Received: 12 May 2017 / Revised: 29 November 2017 / Accepted: 9 December 2017 © 2018 AOCS 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 coro- nary syndrome (ACS) susceptibility. Two CETP gene polymorphisms (rs4783961 and rs708272) and one LCAT polymorphism (rs2292318) were genotyped by 5 0 exonuclease TaqMan assays in 619 patients with ACS and 607 control individuals. For HDL analysis, a sub- group 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 [pC Dom ] = 0.036). The linkage dis- equilibrium analysis showed that one of the eight possi- ble combinations was associated with the risk of developing ACS (OR = 1.52, pC = 0.02), which sug- gests that it may contribute to coronary atherosclerosis. The rs708272 G allele carriers had a lower concentra- tion of cholesterol associated with the HDL2a and HDL3a subclasses when compared with subjects carry- ing 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 signi ficantly 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. Keywords Atherosclerosis  genetics  high-density lipoprotein Lipids (2018) 53: 157–166. Abbreviations ACS acute coronary syndrome CETP cholesteryl ester transfer protein HDL-C high-density lipoprotein-cholesterol LCAT lecithin cholesterol acyltransferase LDL low-density lipoprotein-cholesterol SNP single nucleotide polymorphism T2DM type 2 diabetes mellitus Electronic supplementary material The online version of this article (doi:10.1002/lipd.12017) contains supplementary material, which is available to authorized users. * Jose Manuel Fragoso mfragoso1275@yahoo.com.mx 1 Department of Molecular Biology, Instituto Nacional de Cardiología Ignacio Chávez, 14080 Mexico City, Mexico 2 Atherosclerosis Study Group, Instituto Nacional de Cardiología Ignacio Chávez, 14080 México City, Mexico 3 Interventional Cardiology, Instituto Nacional de Cardiología Ignacio Chávez, 14080 Mexico City, Mexico 4 Department of Endocrinology, Instituto Nacional de Cardiología Ignacio Chávez, 14080 Mexico City, Mexico 5 Department of Experimental Medicine, Hospital General de Mexico, Dr. Eduardo Liceaga, Mexico City, Mexico Present address: Galileo Escobedo, Unit of the Experimental Medicine, Hospital General de Mexico, Dr. Eduardo Liceaga, 06726 Mexico City, Mexico. Lipids (2018) 53: 157–166 DOI 10.1002/lipd.12017 Lipids (2018) 53: 157–166