ATP结合体转运子基因单核苷酸多态性与脑梗死的相关性

The relationship between ABCA1 gene polymorphism and the development of cerebral infarction

目的探讨高密度脂蛋白代谢相关基因ATP结合体转运子(ABCA1)单核苷酸多态性与脑梗死发病的关系。方法调查经CT确诊的脑梗死患者96例,男76例,女20例,平均年龄(59±10)岁;健康对照组90例,男48例,女42例,平均年龄(55±11)岁。提取外周血白细胞全基因组DNA。以聚合酶链式反应(PCR)、限制性片段长度多态性(RFLP)结合测序的方法检测ABCA1 596G→A单核苷酸多态性(SNP)。结果脑梗死及对照组ABCA1-A与G等位基因频率分别为66.1%、33.9%及51.7%和48.3%,两组间等位基因频率分布存在显著性差异(2χ=8.99,P<0.05)。AA基因型与脑梗死发病率增高有关(RR=2.68,95%CI1.5-3.6,P<0.05)。血脂分析提示等位基因A携带者血浆HDL胆固醇水平明显低于等位基因G携带者(1.1±0.3vs.1.3±0.4,P=0.009),而甘油三酯明显升高(2.1±1.2vs.1.8±1.2,P=0.027)。结论ABCA1基因596G→A变异明显会增加脑梗死发病的危险性,其致病机制可能与G→A变异导致HDL降低及TG升高有关。

Objective To explore the risk association between ATP-binding cassette transporter 1 （ATP binding cassette transporter 1, ABCA1 ） genetic polymorphism with the development of cerebral infarction. Methods A total of 96 patients with CT documented cerebral infarction including 76 male and 20 female, aged 59 ±10 years and 90 healthy control including 48 male and 42 female, aged 55± 11 years were included. Fasting vein blood samples of 5 mL were collected for lipid analysis and DNA extraction. The polymerase chain reaction （PCR） ; Restriction fragment length polymorphisms （RFLP） along with sequencing were employed to test single nucleic polymorphisms （SNP） of 596 G to A in ATP Binding Cassette Transporter （ABCA1） gene. Results The A and G aIIelic frequencies of ABCA1 gene were 66.1% and 33.9% in patients group, 51.7% and 48.3% in control group, respectively. The genotypes frequencies varicd significantly between two groups （ X^2=8.99, P〈0.05）. Individuals with AA genotype were more susceptible to cerebral infarction than those with GG genotype （RR =2.68, 95 % CI 1.5- 3.6, P〈0.05）. AA carriers had significantly lower HDL- cholesterol 1.1 ± 0.3 vs. 1.3± 0.4 mmol/L, P= 0. 009） and higher triglyceride level （2.1±1.2 vs.1.8±1.2, P=0.027） than GG carriers. Conclusion ABCA1 G to A variants significantly increases the risk of developing cerebral infarction, which might partly contribute to the unfavorable effect of AA genotype on plasma lipids.