Genetics
Two CETP variants are among only seven SNPs confirmed to affect HDL cholesterol in a 384-SNP, 251-gene screen (J Lipid Res 2008)
Original title: Multiple genetic variants along candidate pathways influence plasma high-density lipoprotein cholesterol concentrations
This study screened three hundred eighty-four single nucleotide polymorphisms across 251 genes in pathways potentially relevant to HDL-cholesterol (HDL-C) metabolism, genotyped in 3575 subjects from the Doetinchem cohort examined three times over 11 years, since known genetic variants explain only part of HDL-C variation. Of three hundred fifty-three SNPs in 239 genes that passed quality control, seven were associated with plasma HDL-C at a false discovery rate q-value below 0.05: CETP rs1800777 and rs5882, LPL rs3208305, rs328, and rs268, LIPC rs1800588, and NRIP1 rs2229741. Five additional SNPs showed weaker associations (FDR_q 0.05-0.2). The authors report replication of previous CETP, LPL, LIPC, HNF4A, and APOA5 associations, alongside several interesting new candidate SNPs for HDL-C warranting further evaluation.
Original abstract
The known genetic variants determining plasma HDL cholesterol (HDL-C) levels explain only part of its variation. Three hundred eighty-four single nucleotide polymorphisms (SNPs) across 251 genes based on pathways potentially relevant to HDL-C metabolism were selected and genotyped in 3,575 subjects from the Doetinchem cohort, which was examined thrice over 11 years. Three hundred fifty-three SNPs in 239 genes passed the quality-control criteria. Seven SNPs [rs1800777 and rs5882 in cholesteryl ester transfer protein (CETP); rs3208305, rs328, and rs268 in LPL; rs1800588 in LIPC; rs2229741 in NRIP1] were associated with plasma HDL-C levels with false discovery rate (FDR) adjusted q values (FDR_q) < 0.05. Five other SNPs (rs17585739 in SC4MOL, rs11066322 in PTPN11, rs4961 in ADD1, rs6060717 near SCAND1, and rs3213451 in MBTPS2 in women) were associated with plasma HDL-C levels with FDR_q between 0.05 and 0.2. Two less well replicated associations (rs3135506 in APOA5 and rs1800961 in HNF4A) known from the literature were also observed, but their significance disappeared after adjustment for multiple testing (P = 0.008, FDR_q = 0.221 for rs3135506; P = 0.018, FDR_q = 0.338 for rs1800961, respectively). In addition to replication of previous results for candidate genes (CETP, LPL, LIPC, HNF4A, and APOA5), we found interesting new candidate SNPs (rs2229741 in NRIP1, rs3213451 in MBTPS2, rs17585739 in SC4MOL, rs11066322 in PTPN11, rs4961 in ADD1, and rs6060717 near SCAND1) for plasma HDL-C levels that should be evaluated further.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.