BACKGROUND: Polymorphism of apolipoprotein A1/C3/A4/A5 gene cluster affected lipid profiles in general population. We reported 6 polymorphisms, APOA1 -75G>A, APOA1 83C>T, APOC3 3175C>G, APOC3 3206G>T, APOA4 127A>G, and APOA5 553G>T in APOA1/C3/A4/A5 gene and the haplotype structures on triglyceride and HDL traits among ethnic Chinese. RESULTS: Overall, there were statistically significant differences in the distribution of APOA1 -75G>A and APOA5 +553G>T genotypes comparing cases with control subjects. For the APOA1 -75 SNP, a lower risk of triglyceride/HDL among subjects with A/A genotype compared with those with the G/G genotype (odds ratio, OR=0.39, 95% CI 0.16-0.92, P=0.04). However, the risk magnitude reduced after multivariate adjustments. For continuous traits, we found that only in APOA5 +553 T allele carriers showed a significant higher triglyceride and a significant lower HDL cholesterol level than subjects with APOA5 +553 G/G genotypes. There were significant differences in overall haplotype frequencies between case and control subjects (P<0.001). CONCLUSION: There is an important role of APOA1/C3/A4/A5 gene polymorphisms and haplotypes in the development of high triglyceride/HDL ratio in Chinese.