Elevation in plasma triglycerides (TG) has been widely accepted as a coronary artery disease (CAD) risk predictor. Recently, a new apolipoprotein playing an important role in TG metabolism named apolipoprotein AV (apoAV) was discovered, which is encoded by the APOA5 gene. Several single nucleotide polymorphisms (SNPs) of APOA5 associated with increased TG concentrations have been identified. We here report that a recently identified genetic variant, c.553G>T in the APOA5 gene which causes a substitution of a cysteine for a glycine residue at amino acid residue 185(G185C) is also associated with increased TG levels. To investigate the association between this genetic variation and the risk of CAD, a case-control study comprising 232 patients with CAD and 302 controls from the same area of China was performed. The minor allele frequencies of c.553G > T for the CAD and control groups were 7.76 and 3.97%, respectively (P = 0.008). In both the CAD and control groups, the T allele carriers had higher serum TG levels than homozygous carriers of the major G allele (CAD group: 2.67 +/- 1.48 mmol/l versus 1.95 +/- 1.02 mmol/l, P = 0.021; controls: 2.31 +/- 1.20 mmol/l versus 1.68 +/- 0.95 mmol/l, P = 0.002). After adjustment for age, gender, body mass index, smoking status, glucose and presence of hypertension, the odds ratio (OR) for CAD in the T allele carriers was 2.089 (95% CI = 1.140-3.830, P = 0.017), in comparison to the individuals without the T allele. These results suggest that the APOA5 c.553G > T polymorphism is an important predictor for hypertriglyceridemia and CAD.