gms | German Medical Science

High density lipoprotein cholesterol (HDL-C) is a risk factor for atherosclerosis. It has antiatherogenic properties and is involved in the reverse transport of cholesterol from cells of the arterial wall to the liver and steroidogenic organs where it is metabolized. There is strong evidence that HDL-C is under significant genetic control. Several but not all genes involved in the regulation of HDL-C plasma concentrations were identified in the past. To identify yet unknown genes influencing HDL-C levels, we performed a genome-wide association study in 1644 individuals from the population-based KORA/MONICA Augsburg. These participants were genotyped using the 500K SNP array (GeneChip Human Mapping 500K set from Affymetrix). HDL-C was analyzed as a continuous quantitative trait using linear regression analysis assuming an additive or a recessive model and with various adjustement of the data. Our systematic review of the literature identified 10 genes for which at least two previous association studies reported significant associations. Four of these genes were identified in this whole genome association studies. Furthermore, we identified 8 and 45 SNPs with p-values <10-5 for the additive and recessive model, respectively, located in genes as of yet undescribed for HDL-C. Additional 39 and 60 SNPs showed p-values between 10-5 and 10-4 for the two models. In a second step, the most promising 13 SNPs, which were not located in the area of the four "re-discovered" candidate genes, were genotyped in further 4000 population-based subjects from the KORA Survey S4. One of this SNPs showed again a clear association with HDL-C levels and will be followed in replication studies. This GWA study identified four out of ten well known genes for HDL-C levels which is a proof of principle, and provided some evidence for a further gene related to HDL-C levels, which has to be verified in further replication studies.