Background: Cardio-cerebrovascular disease is a major public health issue worldwide, and its complex pathogenesis has not been fully elucidated yet.
Objectives: This study was to evaluate the associations between three common polymorphisms (rs11216158, rs670, and rs12721026) in apolipoprotein A1 (APOA1) gene and the lipid-lowering efficacy of statin in a Chinese population with dyslipidemia.
Methods: By the extreme sampling method, we selected the low responders (n=108) and high responders (n=106) based on the adjusted lipid-lowering response residuals to statin after 8-week consecutive medication. Rs11216158, rs670, and rs12721026 loci were genotyped by MALDI-TOF MS platform. Serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were measured at baseline and after 8-week treatment with oral 20 mg/d tablet of simvastatin.
Results: The frequency distributions of rs11216158 and rs670 polymorphisms in the APOA1 gene were significantly different between the low and high responders (P = 0.018 and P = 0.033, respectively). As compared to GG genotype, rs11216158 GA or GA+AA carriers had significantly higher change in HDL-C (ΔHDL-C) (GA: β = 0.13, P = 0.006; or GA+AA: β = 0.12, P = 0.021, respectively) and lower change in LDL-C (ΔLDL-C) (GA: β = -0.33, P = 0.026; or GA+AA: β = -0.27, P = 0.058, respectively). The similar pattern for rs670 locus was observed as well. Both rs11216158 and rs670 are in high linkage disequilibrium (LD). An additive-scale interaction between rs11216158 (or rs670) and obesity was found (both P for interaction = 0.011). In patients with BMI < 25 Kg/m2, the carriers with rs11216158 (or rs670) GA+AA had significantly higher ΔHDL-C (GA+AA: β = 0.18, P = 0.002) after treatment than those with GG genotype, but no difference between them in those with BMI ≧ 25 Kg/m2.
Conclusions: Our major findings suggested that the rs11216158 and rs670 polymorphisms in the APOA1 gene could be important genetic determinants of statin therapeutic efficacy. Genotype-by-obesity interactions also exist on efficacy of statin. It will be helpful for the understanding of the strategy of personalized medicine in Chinese patients with dyslipidemia.
