Scordo Maria Gabriella, Dahl Marja-Liisa, Spina Edoardo, Cordici Francesco, Arena Maria Grazia
Department of Medical Sciences, Clinical Pharmacology, University of Uppsala, Akademiska sjukhuset, Ing. 61, 75185 Uppsala, Sweden.
Pharmacol Res. 2006 Feb;53(2):162-5. doi: 10.1016/j.phrs.2005.10.005. Epub 2005 Dec 6.
Allelic variation at the CYP2D6 gene has been suggested to be associated with CNS disorders, including Parkinson's disease and Lewy body dementia. In order to elucidate whether a relationship exists between CYP2D6 polymorphism and the risk of developing Alzheimer's disease (AD), CYP2D6 allele and genotype frequencies have been evaluated in 94 patients from Southern Italy (29 men and 65 women, aged 74+/-8 years) with AD, and in 350 healthy controls (204 men, 146 women, aged 33+/-9 years) from the same geographical region. Allele frequencies among AD patients were not significantly different from those in healthy controls. Subjects could be divided in four CYP2D6 genotype groups: 52 (56%) patients and 205 (59%) controls carried no mutated alleles (homozygous extensive metabolizers (EM)), 33 (35%) patients and 109 (31%) controls carried one mutated allele (heterozygous EM), while 4 (4%) patients and 11 (3%) controls were found to have two mutated alleles (poor metabolizers (PM)). Five (5%) patients and 25 (7%) controls carried extra copies of a functional gene (ultrarapid metabolizers (UM)). Our results indicate that CYP2D6 polymorphism is unlikely to represent a major risk factor in susceptibility to Alzheimer's disease.
有人提出，细胞色素P450 2D6（CYP2D6）基因的等位基因变异与中枢神经系统疾病有关，包括帕金森病和路易体痴呆。为了阐明CYP2D6基因多态性与患阿尔茨海默病（AD）风险之间是否存在关联，我们对来自意大利南部的94例AD患者（29名男性和65名女性，年龄74±8岁）以及来自同一地理区域的350名健康对照者（204名男性，146名女性，年龄33±9岁）的CYP2D6等位基因和基因型频率进行了评估。AD患者的等位基因频率与健康对照者相比无显著差异。受试者可分为四个CYP2D6基因型组：52例（56%）患者和205例（59%）对照者无突变等位基因（纯合子广泛代谢者（EM）），33例（35%）患者和109例（31%）对照者携带一个突变等位基因（杂合子EM），而4例（4%）患者和11例（3%）对照者有两个突变等位基因（慢代谢者（PM））。5例（5%）患者和25例（7%）对照者携带功能基因的额外拷贝（超快代谢者（UM））。我们的结果表明，CYP2D6基因多态性不太可能是阿尔茨海默病易感性的主要危险因素。
