胆固醇24-羟化酶与ATP结合盒转运蛋白A1基因多态性与阿尔茨海默病的相关性

[Correlation of cholesterol 24-hydroxylase and ATP-binding cassette transporter A1 polymorphisms with Alzheimer's disease].

作者信息

Wang Fen, Jia Jian-Ping

机构信息

Department of Neurology, Xuanwu Hospital of Capital University of Medical Sciences, Beijing 100053, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2007 Mar 6;87(9):614-8.

PMID:17550732

Abstract

OBJECTIVE

To investigate the association of the single nucleotide polymorphisms (SNPs) A-->G in the intron 2 of cholesterol 24-hydroxylase (CYP46) gene and G-->A (R219K) in the exon 6 of ATP-binding 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 genotypes. 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%, chi(2) = 19.060, P < 0.01). The risk of SAD in those with at least one epsilon 4 allele was 2.8 times that in those without epsilon 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 (chi(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%, chi(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 genotype carriers by 60% (adjusted OR = 0.40; 95% CI = 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 ABCA1 gene may have a protective effect for AD in Han Chinese.

摘要

目的

研究胆固醇24 - 羟化酶（CYP46）基因内含子2的单核苷酸多态性（SNP）A→G以及ATP结合盒转运体A1（ABCA1）基因外显子6的G→A（R219K）与汉族人群散发性阿尔茨海默病（SAD）的相关性。

方法

收集168例SAD患者的外周血样本，其中男性74例，女性94例，年龄74±8（52 - 95）岁，平均发病年龄69±7（47 - 86）岁，并选取215例性别和年龄匹配的健康人作为对照。采用聚合酶链反应 - 限制性片段长度多态性（PCR - RFLP）方法检测基因型。进行载脂蛋白E（ApoE）基因分型。评估多态性与AD之间的关联强度。

结果

SAD患者ApoE基因型频率为14%，显著高于对照组（5.1%，χ² = 19.060，P < 0.01）。至少携带一个ε4等位基因的SAD患者发病风险是不携带ε4等位基因患者的2.8倍（OR = 2.82，95%可信区间 = 1.54 - 5.17，P = 0.001）。SAD患者与对照组之间CYP46基因的基因型或等位基因频率无显著差异。然而，ABCA1基因多态性与SAD之间存在明显关联（χ² = 8.230，P = 0.016）。SAD患者中G/A + A/A基因型频率为61.3%，显著低于对照组（73.5%，χ² = 6.444，P = 0.011）。A等位基因携带者（G/A + A/A基因型）患SAD的风险比GG基因型者显著低43%（校正OR = 0.57，95%可信区间 = 0.36 - 0.91，P = 0.019），AA纯合子携带者患SAD的风险比GG基因型携带者显著低60%（校正OR = 0.40；95%可信区间 = 0.21 - 0.77，P = 0.006）。