胆固醇24S-羟化酶和三磷酸腺苷结合盒转运子A1基因多态性与阿尔茨海默病的相关性分析

Correlation of cholesterol 24-hydroxylase and ATP-binding cassette transporter AI polymorphisms with Alzheimer's disease

目的探讨胆固醇24S-羟化酶(CYP46)基因第二内含子 A→G多态性位点和三磷酸腺苷结合盒转运子 A1(ABCA1)基因第六外显子 G→A(R219K)多态性位点与散发性阿尔茨海默病(SAD)易感性的关系。方法采用病例-对照研究方法,利用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术对168例 SAD 患者和215名正常对照的 CYP46和 ABCA1基因多态性进行检测,比较不同基因型与阿尔茨海默病(AD)发病风险之间的关系。结果 CYP46基因第二内含子 A→G多态性等位基因频率和基因型分布在 SAD 组和正常对照组差异无统计学意义。ABCA1基因第六外显子 G→A多态性的基因型分布在两组之间差异有统计学意义(x^2=8.230,P=0.016),AD 组携带 A等位基因(G/A+A/A 基因型)的频率明显低于对照组(61.3%vs 73.5%,x^2=6.444,P=0.011)。Logistic 回归分析表明携带 A 等位基因者(G/A+A/A 基因型)比携带 GG 基因型者 AD 发病风险低43%(校正后 OR=0.57,95%CI=0.36～0.91,P=0.019),而 AA 纯合子比携带 GG 基因型者 AD 发病风险低60%(校正后 OR=0.40,95%CI=0.21～0.77,P=0.006)。结论 CYP46第二内含子 A→G多态性可能与 AD 发病无关;而 ABCA1基因第六外显子 G→A多态性与 SAD 相关,携带 A 等位基因或 AA 基因型对 SAD 发病可能有一定的保护作用。

Objective To investigate the association of the single nucleotide polymorphisms （SNPs） A→G in the intron 2 of cholesterol 24-hydroxylase （CYP46） gene and C→A （R219K） in the exon 6 of ATP-hinding cassette transporter A1 （ABCA1） gene with sporadic Alzheimer＇s disease （SAD） in the Han Chinese population. Methods Peripheral blood samples were collected from 168 SAD patients, 74 males and 94 females, aged 74 ± 8 （52 - 95 ）, with an average age at onset of 69 ±7 （47 - 86 ）, and sex-, and age-matched 215 healthy persons. PCR-restriction fragment length polymorphism （PCR-RFLP） was used to detect the genotypos. Apolipoprotein E （ApoE） genotyping was conducted. The strength of association between the polymorphisms and AD was estimate. Results The frequency of ApoE genotype of the SAD patients was 14%, significantly higher than that of the controls （5.1%, X^2 =19.060, P〈0.01）. The risk of SAD in those with at least one ε4 allele was 2.8 times that in those without e 4 allele （ OR = 2. 82, 95% CI = 1.54-5. 17, P = 0. 001 ）. There was no significant difference in the genotype or allele frequencies for CYP46 gene between the SAD patients and controls. However, there was an obvious association between the polymorphism of ABCA1 gene and SAD （ X^2 = 8.230, P = 0.016）. The frequency of G/A ＋ A/A genotypes in the SAD patients was 61. 3%, significantly lower than that of the controls （73.5%, X^2 = 6. 444, P = 0.011 ）. The risk of SAD in the carriers of A alleles （ G/A ＋ A/A genotypes） was significantly lower than those with GG genotype by 43% （adjusted OR =0.57, 95% CI =0. 36-0. 91, P=0.019）, and the risk of SAD in the AA homozygote carriers was significantly lower than that of the GG genotypecarriers by60% （adjusted OR=0.40; 95% C1=0.21-0.77, P=0.006）. Conclusion The CYP46 intron 2 polymorphism may not be associated with the risk of AD, but AA genotype or A allele of ABCAI gene may have a protective effect for AD in Hart Chinese.