Deng Jinfeng, Deng Yanyao, Li Wei, Feng Xialu, Yu Zhuling, Zhao Yan, Hou Deren
Department of Neurology, Third Xiangya Hospital, Central South University, Changsha 410013, China.E-mail:
Nan Fang Yi Ke Da Xue Xue Bao. 2015 Aug;35(9):1325-30.
To determine the association between the polymorphism of angiotensin converting enzyme (ACE) gene and Alzheimer's disease (AD).
This case-control study involved 201 AD patients and 257 healthy subjects matched for age and gender as the control group. Polymerase chain reaction amplification and matrix-assisted laser desorption/ ionization time of flight mass spectrometry were used to examine the rs4291, rs4309, and rs4343 of ACE gene, and the difference in genotypes, allelotype frequencies and haplotype frequencies were analyzed between the two groups.
No statistic difference was found in the genotype and allelotype frequencies of rs4291 locus between AD and control groups (P>0.05). A significant difference was found in the genotype and allelotype frequencies of rs4309 between the two groups with a significant increase in the C allelotype frequency in AD group (OR=1.917, 95% CI=1.431-2.568, P<0.05). The difference in the genotype frequency of rs4343 was not significant between the two groups, but the allelotype frequencies differed significantly with a decreased A allelotype frequency in AD group(OR=0.714, 95% CI=0.532-0.957, P=0.024). Analysis of the linkage disequilibrium among the loci of rs4291, rs4309 and rs4343 showed a D' all above 0.65 between one another. Haplotype analysis confirmed the existence of 5 haplotypes, namely ATA, ACA, TCA, TCG and TTG, indicating a negative correlation between haplotype ATA and AD occurrence (OR=0.558, 95% CI=0.420-0.741, P<0.05) and positive correlations of haplotype ACA and TCA with AD occurrence (ACA: OR=4.883, 95% CI=2.267-10.518, P<0.05; TCA: OR=2.269, 95% CI=1.083-4.754, P<0.05).
The polymorphism of rs4291 may have no relation with the incidence of AD. Polymorphisms of s4309 and rs4343 may be related to AD, and ATA, ACA and TCA haplotypes composed of rs4291/rs4309/rs4343 may be related to AD.
确定血管紧张素转换酶(ACE)基因多态性与阿尔茨海默病(AD)之间的关联。
本病例对照研究纳入201例AD患者及257例年龄和性别相匹配的健康受试者作为对照组。采用聚合酶链反应扩增及基质辅助激光解吸/电离飞行时间质谱法检测ACE基因的rs4291、rs4309和rs4343位点,并分析两组间基因型、等位基因频率及单倍型频率的差异。
AD组与对照组rs4291位点的基因型及等位基因频率差异无统计学意义(P>0.05)。两组rs4309位点的基因型及等位基因频率差异有统计学意义,AD组C等位基因频率显著升高(OR=1.917,95%CI=1.431-2.568,P<0.05)。rs4343位点的基因型频率在两组间差异无统计学意义,但等位基因频率差异有统计学意义,AD组A等位基因频率降低(OR=0.714,95%CI=0.532-0.957,P=0.024)。rs4291、rs4309和rs4343位点间的连锁不平衡分析显示,两两之间的D'均大于0.65。单倍型分析证实存在5种单倍型,即ATA、ACA、TCA、TCG和TTG,表明单倍型ATA与AD发生呈负相关(OR=0.558,95%CI=0.420-0.741,P<0.05),单倍型ACA和TCA与AD发生呈正相关(ACA:OR=4.883,95%CI=2.267-10.518,P<0.05;TCA:OR=2.269,95%CI=1.083-4.754,P<0.05)。
rs4291多态性可能与AD发病率无关。rs4309和rs4343多态性可能与AD有关,由rs4291/rs4309/rs4343组成的ATA、ACA和TCA单倍型可能与AD有关。