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

目的探讨胆固醇24S-羟化酶（CW46）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-RVLV）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％vs73．5％,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）,而从纯合子比携带GG基因型者AD发病风险低60％（校正后OR=O．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等位基因或从基因型对SAD发病可能有一定的保护作用。

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

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.