Variation in the APOA5 gene has been shown to be associated with triglyceride levels in several independent population studies. It was our objective to determine if a relationship existed between selected genotypes or haplotypes of the APOA5 gene and findings on selective coronary angiography (SCA) in an independent cohort. The Vancouver SCA Cohort consists of individuals referred for angiography between 1993 and 1995. DNA was extracted from 537 patients and analyzed for the -1131T>C and the c.56C>G polymorphisms which define three common haplotypes of the APOA5 gene. Plasma triglycerides and the fractional esterification rate in apoB-depleted lipoproteins (FER(HDL)), an index of high-density lipoprotein (HDL) composition, were significantly higher (P = 0.01 and P = 0.001, respectively), and HDL cholesterol (HDL-C) was significantly lower (P = 0.03) in Caucasians with genotypes containing the minor allele of the -1131T>C polymorphism compared to the homozygotes for the major allele. However, there was no relationship between the c.56C>G polymorphism of the APOA5 gene and any of the measured lipid and lipoprotein parameters. Subjects homozygous for the common haplotype APOA5*1 had decreased triglyceride levels and FER(HDL) (P = 0.04 and P < 0.001, respectively) and increased HDL-C levels (P = 0.01) compared to subjects with all other haplogenotypes. Multivariate linear regression analysis indicated that the -1131T>C polymorphism remained an independent predictor of triglyceride, HDL-C, and FER(HDL) following adjustment of several variables including age, gender, body mass index, diabetes, lipid lowering and beta-blocker medication. The APOA5*1/*1 haplogenotype remained an independent predictor of HDL-C and FER(HDL) following adjustment of the same variables. The relationship between APOA5 genotype or haplogenotype and FER(HDL) remained significant even after the addition of both HDL-C and triglyceride to the model. However, there was no association between APOA5 gene polymorphisms or haplotypes and coronary artery disease as determined by angiography.