Effests Of ABCA1 And MTP Gene Polymorphism On The Lipide-regulating Efficacy Of Simvastatin

Object To investigate the effect of ABCA1-R2K and MTP- Q3H gene polymorphism on hyperlipemia and the lipide-regulating efficacy of Simvastatin. To explore the genetics mechanism of the lipide-regulating efficacy individualization difference of Simvastatin.Methods 123 cholesterolema patients are enrolled to peros continuously Simvastatin 20mg perp day for 8 weeks. The TC, TG, LDL-C and HDL-C were measured before treatment and 4, 8 weeks of treatment.The polymorphism of ABCA1-R2K and MTP- Q3H gene were determined by TaqMan method.Results The frequency of ABCA1-R2K polymorphism is 39.8% in RR genotype, 45.5% in RK genotype and 14.6% in KK genotype. The frequency of MTP- Q3H polymorphism is 43.1% in QQ genotype, 46.3% in QH genotype and 10.6% in HH genotype. The serum levels of TC and LDI-C were significantly decrease after 8 weeks Simvastatin therapy in the three genotype groups of ABCA1-R2K and MTP- Q3H. The decrease range of TC in mutation homozygote was much less than the other genotype .The KK homozygote of ABCA1-R2K is predominance in woman,but it is predominance in man in The HH homozygote of MTP- Q3H. The results from multiple linear regression analysis showed that ABCA1-R2K and MTP- Q3H genotype were the susceptible factors of simvastatin intervention. The conclusions could be primarily drawn that the variants of ABCA1-R2K and MTP- Q3H were important determinants of variation in serum cholesterol response to simvastatin in cholesterolema population.Conclusion These findings suggest that ABCA1-R2K polymorphism and MTP- Q3H polymorphism are the markers which may predict thehydroxy-methyl-glutaryl coenzyme A reductase inhibitors' therapeutic effect in patients with high cholesterolemia.