Potentially protective effects of the Ser447-Ter mutation of the lipoprotein lipase gene against the development of coronary artery disease in Japanese subjects via a beneficial lipid profile

Several DNA variants at the lipoprotein lipase (LPL) gene locus have been f ound to be associated with the plasma lipid levels and the prevalence of co ronary artery disease (CAD). In particular, the Ser447-termination (Ter) mu tation at the exon 9 of the LPL gene has the potential to elevate the plasm a high-density lipoprotein (HDL) levels, but it remains unknown in the Japa nese population. The present study investigated 93 CAD patients and 96 age- and sex-matched healthy controls. The Ser447-Ter mutation was determined b y polymerase chain reaction restriction fragment length polymorphism method . The allelic frequency of the Ser447-Ter mutation was 0.103 in all subject s. The Ser447-Ter (GG and CG) group was associated with significantly highe r levels of plasma HDL-cholesterol (p<0.001) and lower levels of plasma tri glyceride than the CC group (p<0.02). The peak particle size of low-density lipoprotein (LDL) was significantly larger in the Ser447-Ter (GG and CG) g roup than in CC group (p<0.05). The frequency of the Ser447-Ter genotype in GG and CG was significantly lower in CAD than in the controls (11.9% vs 26 %, odds ratio = 0.38; 95% confidence interval, 0.18-0.81; p<0.02). These re sults suggest that the Ser447-Ter mutation of the LPL gene is associated wi th high plasma HDL-cholesterol levels, low plasma triglyceride levels and a larger LDL particle size. This mutation may have a protective effect again st the development of CAD via its favorable lipoprotein profile.