Mattila K M, Rinne J O, Röyttä M, Laippala P, Pietilä T, Kalimo H, Koivula T, Frey H, Lehtimäki T
Department of Clinical Chemistry, Centre for Laboratory Medicine, Tampere University Hospital, Finn-Medi 2, Third Floor, PO Box 2000, FIN-33521 Tampere, Finland.
J Med Genet. 2000 Oct;37(10):766-70. doi: 10.1136/jmg.37.10.766.
Alzheimer's disease (AD) and Parkinson's disease (PD) are genetically heterogeneous. Dipeptidyl carboxypeptidase 1 (DCP1) and butyrylcholinesterase (BCHE) genes may modify the risk of these disorders. We investigated whether common polymorphisms present in these genes operate as risk factors for AD and PD in Finnish subjects, independently or in concert with the apolipoprotein E epsilon4 allele (APOE epsilon4). Eighty late onset sporadic AD patients, 53 PD patients (34 of whom had concomitant AD pathology), and 67 control subjects were genotyped for the insertion (I)/deletion (D) polymorphism of DCP1 and the K variant of BCHE. In logistic regression analysis, the DCP1 *I allele in combination with APOE epsilon4 significantly increased the risk of AD (OR 30.0, 95% CI 7.3-123.7), compared to subjects carrying neither of the alleles. Similar analysis showed that the risk of AD was significantly increased in subjects carrying both the BCHE wild type (*WT/*WT) genotype and epsilon4 (OR 9.9, 95% CI 2.9-33.8), compared to those without this BCHE genotype and epsilon4. Further, the risk of PD with AD pathology was significantly increased for carriers of DCP1 *I and epsilon4 (OR 8.0, 95% CI 2.1-31.1). We thus conclude that, in Finns, interaction between DCP1 *I and epsilon4 increases the risk of AD as well as of PD with coexisting Alzheimer pathology, which underlines the importance of the DCP1 I/D polymorphism in the development of Alzheimer neuropathology, whereas the wild type BCHE genotype in combination with epsilon4 had a combined effect with regard to the risk of AD.
阿尔茨海默病（AD）和帕金森病（PD）在遗传上具有异质性。二肽基羧肽酶1（DCP1）和丁酰胆碱酯酶（BCHE）基因可能会改变这些疾病的风险。我们研究了这些基因中存在的常见多态性是否独立或与载脂蛋白Eε4等位基因（APOEε4）协同作用，作为芬兰人群中AD和PD的风险因素。对80例晚发性散发性AD患者、53例PD患者（其中34例伴有AD病理改变）和67例对照受试者进行了DCP1插入（I）/缺失（D）多态性和BCHE的K变异体基因分型。在逻辑回归分析中，与既不携带这两个等位基因的受试者相比，DCP1 *I等位基因与APOEε4联合显著增加了AD风险（比值比30.0，95%可信区间7.3 - 123.7）。类似分析表明，与不携带这种BCHE基因型和ε4的受试者相比，携带BCHE野生型（*WT/*WT）基因型和ε4的受试者AD风险显著增加（比值比9.9，95%可信区间2.9 - 33.8）。此外，携带DCP1 *I和ε4的患者发生伴有AD病理改变的PD风险显著增加（比值比8.0，95%可信区间2.1 - 31.1）。因此，我们得出结论，在芬兰人群中，DCP1 *I与ε4之间的相互作用增加了AD以及伴有共存阿尔茨海默病理改变的PD风险，这突出了DCP1 I/D多态性在阿尔茨海默神经病理学发展中的重要性，而野生型BCHE基因型与ε4联合对AD风险具有综合作用。
