To determine whether the integrative variants, haplotypes and diplotypes of the calpain 3 (CAPN3) and the FERM domain containing 5 genes (FRMD5) and several environmental exposures are associated with an implication in lipid homeostasis, which are associated with cardiovascular risk. Genotyping of the CAPN3 rs4344713 and FRMD5 rs524908 was performed by Sanger sequencing in 1,640 subjects (Jing, 819 and Han, 821). Multivariate analyses of covariance models that adjusted by age, gender, body mass index (BMI), blood pressure and lifestyle (smoking and drinking), were constructed using variants, haplotypes and diplotypes of the CAPN3 rs4344713 and FRMD5 rs524908 as predictors and changes in lipid variables. Significant associations with low-density lipoprotein cholesterol and apolipoprotein (Apo) B were found. Linkage disequilibrium with each other showed the haplotype-phenotype associations with triglyceride and ApoA1. This study also suggested pleiotropic associations of the CAPN3-FRMD5 diplotypes with lipid variables. As potential confounders, diastolic blood pressure (DBP) and BMI were significantly associated with lipid variables. We conclude that integrative variants, haplotypes and diplotypes of the CAPN3 rs4344713 and FRMD5 rs524908, as well as DBP and BMI are associated with serum lipid variables in the Jing and Han populations.