换瓣术后华法林维持量与mEH ApoE基因多态性的相关性研究

目的探讨mEH基因T612C、A691G位点sNP及ApoE基因型在中国汉族人群中的分布，并探讨华法林维持剂量与其相关性。方法共选取52例换瓣术后患者以及68例健康汉族个体。瓣膜置换术后个体根据国际化标准比值（INR）控制在1．5～2．2，调整华法林维持剂量，采用PCR-RFLP技术检测ApoE基因型、Pyrosequencing法检测mEHT612C及A691GSNP。结果（1）在120个受测试人群中，mEHT612C等位基因频率分别为74．6％和25．4％；而mEHA691G分别为66．7％、33．3％，换瓣人群中mEHT612C的纯合子比杂合子和野生型的所需华法林剂量要高，分别为（5．5±2．9）mg／d、（4．8±2．2）mg／d、（4．0±2．6）mg／d，三者之间剂量比较有显著性差异（P〈0．05）。（2）在120个受测试人群中，ApoE基因型等位基因E2，E3，E4的频率分别为44．2％、35．8％、20．O％；换瓣人群中各基因型所需华法林的剂量分别为（4．5±2．7）mg／d、（4．7±2．4）mg／d、（4．4±2．6）mg／d，三者之间差异无统计学意义（P〉0．05）。结论mEH基因T612C、A691G位点SNP能解释部分个体之间华法林维持剂量的差异，ApoE基因型的差异不能解释华法林维持剂量的差异。

Objective To explore the relationship between warfarin maintain dose with single nucleotide polymorphisms for gene mEH and genotype of ApoE, also to Discussion on the distribution of Chinese Hart population. Methods A total of 50 cases were selected after valve replacement patients and 50 cases of healthy Hart individuals. Warfarin maintain dose was adjusted to the low anticoagulant level in which the INR was between 1.5 and 2.2.The polymorphisms of ApoE was detected using PCR-RFLP method; single nucleotide polymorphisms on T612C and A691G for gene mEH was detected using pyrosequeneing method. Results 1. On the test group, Allele frequencies ofmEH on T612C were 71.2% and 28.8%; on A691G were 67.3% and 32.7%. Among valve replacement cases, Homozygotes of mEH T612C required higher warfarin dose than heterozygous and wild type, were 5.5±2.gmg, 4.8± 2.2mg, 4 ± 2.6rag/d, between the three doses had significant difference, （P〈0.05） . 2.On the test group, the ApoE genotype alleles E2, E3, E4 frequencies were 21%, 53%, 26%; Among valve replacement populations, required warfarin doses of different genotypes were 4.5 ± 2.7mg, 4.7± 2.4mg, 4.4 ±2.6rag/d, no significant difference were found, （ P〉0.05 ） . Conclusion Single nucleotide polymorphism on mEH T612C and A691G loci gene can explain part of individual difference on warfarin maintenance dose, but ApoE genotype difference can not explain the difference on warfarin maintenance dose.