In the United States, coronary heart disease (CHD) is the most common cause of death and number one killer of American males and females. Several risk factors for CHD have been identified, including low high-density lipoprotein cholesterol (HDL-C), elevated total cholesterol and low-density lipoprotein cholesterol (LDL-C), and high triglycerides (TG), but the genetic variations underlying inter-individual differences in plasma lipid profiles still need to be further explored. Thus, our interest has been focused on the lipoprotein lipase ( LPL ) which is one of the major genes involved in lipid metabolism. Previously, its sequence variation has been associated with the risk of CHD and other complex traits such as dyslipidemia, type 2 diabetes, essential hypertension, and Alzheimer’s disease. In order to further investigate the common and rare variation in LPL , we resequenced the 95 individuals having lower (n=48) and upper (n=48) 5 th percentiles of HDL-C levels selected from a well defined population-based non-Hispanic White (NHW) sample of 623 individuals. As a result of resequencing the entire LPL gene and additional 1kb at the 5’ and 3’ end, a total of 179 variants (substitutions or indels) plus one microsatellite were identified, including 91 relatively uncommon or rare variants [minor allele frequency (MAF) LPL gene in regulation of plasma HDL-C levels and other lipids.