出版社：American Society for Biochemistry and Molecular Biology
摘要：The cholesteryl ester transfer protein gene (CETP) has beenthe subject of hundreds of genetic analyses that typically focuson a small number of polymorphisms within a single ethnic group.Furthermore, the extent of DNA beyond the transcribed sequencefrom which single nucleotide polymorphisms (SNPs) may influenceCETP expression has not been well defined. To better understandthe role of natural variation in modulating CETP and high densitylipoprotein-cholesterol (HDL-C) levels, dense genotyping ofCETP and regions up to 15 kb on either side of the gene wascarried out on >2,000 individuals. A complex, nonlinear setof linkage disequilibrium bins was found, with many bins interspersedalong the DNA sequence and spread over large regions of thegene. Bins assigned based on large numbers of individuals matchedthe small subset of SNPs that had been assigned to bins previouslywith a small number of individuals. Associations of known functionalSNPs with HDL-C were found, but there were suggestions thatthere are additional functional SNPs not characterized previously.Narrowing of the set of likely functional SNPs was accomplishedby comparing associations observed in different ethnic groups.The promoter SNP most highly associated with HDL-C that is likelyto be functional, position –4,502, alters a consensustranscription factor binding site.Supplementary key words genetics • high density lipoprotein • single nucleotide polymorphism • cholesteryl ester transfer protein
