The UCP2-866 A/A genotype is associated with low density lipoprotein particle sizes in the general population

Background: It has been reported that a common G→A single nucleotide polymorphism (SNP) at the position -866 of the uncoupling protein-2 promoter (UCP2-866 G/ASNP) modulates UCP2 expression in adipose tissue and pancreatic β-cell function, and lipid profiles. Reduced low density lipoprotein (LDL) particle size is a significant predictor of the development for coronary artery disease. The purpose of this study was to investigate whether the UCP2-866 G/A SNP was associated with serum LDL particle characteristics in a general Japanese population. Material/Methods: In 279 subjects (age 65±13 years), body mass index (BMI), percent body fat, blood pressure, and blood biochemical profiles were measured. The UCP2-866 G/A SNP was determined with a fluorescence-based allele-specific DNA primer assay system. LDL particle characteristics were analyzed by high-resolution polyacrylamide gel electrophoresis. Results: The frequency of the -866 A allele was 47.8%. There was no difference in triglyceride, total cholesterol, LDL-cholesterol, HDL-cholesterol, and small dense LDL levels between genotypes. However, subjects with the -866 A/A genotype had significantly lower mean LDL particle size levels (263.5±4.9A) than those with the -866 G/G genotype (264.6±4.9A, P=0.034). Multiple regression analysis revealed that the -866 A/A genotype was a significant variable contributing to the variance in the reduced LDL particle size levels (P=0.012). Conclusions: The -866 A/A genotype may contribute to reduced LDL particle size levels, a significant risk factor for the development of coronary artery disease.