载脂蛋白 E 基因多态性与阿尔茨海默病的相关性研究进展
The polymorphism of the ATP-binding cassette transporter 1 gene modulates Alzheimer disease risk in Chinese Han ethnic population.
机构信息
Department of Neurology and Institute of Neurology, Huashan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, Shanghai, China.
出版信息
Am J Geriatr Psychiatry. 2012 Jul;20(7):603-11. doi: 10.1097/JGP.0b013e3182423b6a.
BACKGROUND
Recent studies highlight a potential role of cholesterol metabolic disturbance in the pathophysiology of Alzheimer disease (AD). The adenosine triphosphate (ATP)-binding cassette transporter 1 (ABCA1) gene resides within proximity of linkage peaks on chromosome 9q influence AD and plays a key role in cellular cholesterol efflux in the brain.
METHODS
We studied the role of R219K and V825I polymorphisms of ABCA1 in modulating the risk of AD in 321 AD patients and 349 comparisons of Chinese Han. Genotyping of R219K and V825I were performed by PCR-restriction fragment length polymorphism analysis.
RESULTS
The genotype distribution of R219K was different with more RK in total AD group (χ(2) = 8.705, df = 2, p = 0.013), late-onset AD (LOAD) group (χ(2) = 10.636, df = 2, p = 0.005), APOE non-ε4ε4 group (χ(2) = 9.900, df = 2, p = 0.007), and female AD group (χ(2) = 8.369, df = 2, p = 0.015). Logistic regression manifested the risk of AD increased in RK carriers in total AD group (Wald = 6.102, df = 1, p = 0.014, odds ratio [OR]: 1.546, 95% confidence interval [95% CI]: 1.094-2.185), LOAD group (Wald = 7.746, df = 1, p = 0.005, OR: 1.921, 95% CI: 1.213-3.041), and APOE non-ε4ε4 group (Wald = 6.399, df = 1, p = 0.011, OR: 1.586, 95% CI: 1.109-2.266). K allele (RK + KK) also increased the risk of AD compared with RR allele in LOAD group (Wald = 4.750, df = 1, p = 0.029, OR: 1.619, 95% CI: 1.050-2.497). However, no discrepancy was found in V825I. In R219K, age at onset (AAO) was significantly lower by 4.9 years on average in patients of KK genotype than those of RK in APOE ε4 carrying group and higher by 5.5 years in patients of KK genotype than those of RR in APOE ε4 noncarrying group. In V825I, AAO was diseased by 4.3 years in II genotype compared with VV genotype in APOE ε4 noncarrying group and 3.4 years in APOE ε4ε4 noncarrying group.
CONCLUSION
The results indicated that the RK genotype or K allele (RK + KK) of R219K may relate to the development of AD in the east of China.
背景
最近的研究强调了胆固醇代谢紊乱在阿尔茨海默病（AD）病理生理学中的潜在作用。三磷酸腺苷（ATP）结合盒转运体 1（ABCA1）基因位于 9 号染色体上与 AD 相关的连锁峰附近，在大脑细胞胆固醇外排中起关键作用。
方法
我们研究了 ABCA1 的 R219K 和 V825I 多态性在调节 321 例 AD 患者和 349 例中国汉族对照者 AD 风险中的作用。通过 PCR-限制性片段长度多态性分析对 R219K 和 V825I 进行基因分型。
结果
R219K 的基因型分布在总 AD 组（χ(2) = 8.705，df = 2，p = 0.013）、迟发性 AD（LOAD）组（χ(2) = 10.636，df = 2，p = 0.005）、载脂蛋白 E 非 ε4ε4 组（χ(2) = 9.900，df = 2，p = 0.007）和女性 AD 组（χ(2) = 8.369，df = 2，p = 0.015）中存在差异。Logistic 回归表明，在总 AD 组（Wald = 6.102，df = 1，p = 0.014，OR：1.546，95%CI：1.094-2.185）、LOAD 组（Wald = 7.746，df = 1，p = 0.005，OR：1.921，95%CI：1.213-3.041）和载脂蛋白 E 非 ε4ε4 组（Wald = 6.399，df = 1，p = 0.011，OR：1.586，95%CI：1.109-2.266）中，RK 携带者的 AD 风险增加。与 RR 等位基因相比，K 等位基因（RK + KK）也增加了 LOAD 组 AD 的发病风险（Wald = 4.750，df = 1，p = 0.029，OR：1.619，95%CI：1.050-2.497）。然而，V825I 中并未发现差异。在 R219K 中，携带 KK 基因型的患者的发病年龄（AAO）比携带 RK 基因型的患者平均低 4.9 岁，而在载脂蛋白 E 非携带者中，携带 KK 基因型的患者的发病年龄比携带 RR 基因型的患者高 5.5 岁。在 V825I 中，与 VV 基因型相比，II 基因型在载脂蛋白 E 非携带者中的发病年龄（AAO）为 4.3 岁，在载脂蛋白 E 非 ε4ε4 携带者中为 3.4 岁。
结论
结果表明，R219K 的 RK 基因型或 K 等位基因（RK + KK）可能与中国东部 AD 的发生有关。
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