Serum triglyceride (TG) level is a good surrogate marker for both free fatty acid and the remnant cholesterol level, which is an emerging risk factor of type 2 diabetes and coronary heart disease respectively. Numerous epidemiologic studies suggested that although Asians are generally less obese, those with overweight condition tend to have more dyslipidemic complications than Caucasians. It is well known that chromosome 11q23.3 region harbors important genes regulating TG, notably apolipoprotein (APO) A1, A4, A5, C3, and also other candidate genes such as BUD13 and ZNF 259. Many genome-wide association studies (GWAS) showed strong signals on 11q23.3 regions, but suggested susceptibility genes have been conflicting between studies or between populations. When we further analyzed the 11q23.3 regions using two population-based genome cohort studies of Koreans, we found multiple susceptibility loci, not one is exerting their effects on TG by conditional analyses, haprotype analyses and GxG interaction analyses. Our findings suggest that at least one variants on proximal of the cluster (BUD13/ZNF259) decrease TG, while two independent variants on APOA5/A4 (distal of the cluster) increase TG. This cluster have different likage disequilibrium structures between European, African and Asian ancestors, When we further investigated GxE interactions on these variants with general and abdominal obesity, several regions showed siginificant GxE intereaction on genome-wide significance level. Combining the findings, we concluded that the Asian-specific characteristics of 11q23.3 regions might explain the different susceptibility to hypertriglyceridemic risk for Asians.