한국인 집단에서 알츠하이머 치매의 임상적 진단을 위한 ApoE 유전자와 BchE-k 변이형과의 상승관계에 관한 연구

Abstract

The Apolipoprotein E type 4 allele (ApoE ε4) is genetically associated with the common late onset familial and sporadic fonns of Alzheimer′s disease. ApoE gene is located on chromosome 19, and the three common alleles are designated ε2, ε3, and ε4. The ε4 gene is a major risk factor for late onset Alzheimer′s disease(LOAD). It has been reported that the polymorphic k variant of butyrylcholinesterase (BchE-k) has an elevated frequency in AD patients carrying the ε4 allele of ApoE when compared with a nonnal healthy group. BchE activity in the brain increases around age 60 and is elevated in AD. The BchE-k variant, which is the common variant of the BchE gene, has been reported to show allelic association with AD in subjects who are also carriers of the ε4 allele of ApoE, especiallyin subjects over the age of 75. This study was perfonned to evaluate the distribution of ApoE and BchE genotype in healthy and AD group and to evaluate the synergy between BchE-k variant and ApoE ε4 in AD. ApoE and BchE genotype were determined in DNA samples from 610 healthy group and 60 LOAD patients by using ARMS allele specific oligonucleotides (ASOs) amplification by standard agarose gel electrophoresis. The efIect of ApoE ε4 was significantly associated with AD(p〈0.05). A comparison between AD patients and the healthy individuals, both with the ε4 allele, indicated an interaction between BchE-k and ApoE ε4(p〈0.05). The association of BchE-k with AD was limited to carriers of ApoE ε4 allele, among whom the presence of BchE-k gave an odds ratio of AD of 3.48 (95% C.I. 1.3-9.2). Together these results suggested that further evidence of an association between ApoE ε4 and LOAD, and BchE-k acts in synergy with ApoE ε4 as a susceptibility gene for AD.