散发性Alzheimer病与神经型尼古丁胆碱能受体α4α7基因多态性的关联研究

Association of genetic polymorphisms of CHRNA4 ,7 with Sporadic Alzheimer's disease

目的探讨散发性Alzheimer病(SAD)与神经型尼古丁胆碱能受体α4亚单位(CHRNA4)基因外显子3、α7亚单位(CHRNA7)基因内含子3、7基因多态性的关联关系。方法用聚合酶链式反应-变性梯度凝胶电泳(PCR-DGGE)和DNA测序技术分析23例SAD患者及30例正常人的CHRNA4基因外显子3基因序列和16例SAD患者及16例正常人CHRNA7基因全部外显子及其两侧的部分内含子基因序列。结果在CHRNA4基因外显子3上发现3个新的多态性位点C104T(2=8,41,P<0.05)、A136G(2=16.21,P<0.05);G169A(2=3.98,P<0.05)。研究结果显示3个多态位点在SAD组与对照组之间存在差异显著性。在CHRNA7基因上发现2个新的多态性位点内含子3G3133418C(2=4.571,P>0.05)、内含子7上117643+GTG三碱基插入突变(2=1.032,P>0.5)统计学结果该2个多态位点在SAD组与对照组之间无差异显著性。结论在CHRNA4基因外显子3上发现的3个新的多态性位点(GeneBank登录号为AY786507AY857199AY857197)与散发性Alzheimer病的发病可能存在相关关系。在CHRNA7基因上发现的2个新的多态性位点(GeneBank登录号为AY641830和AY641831)与散发性Alzheimer病的发病没有显著性的相关关系。因此CHRNA4基因外显子3多态性可能与散发性Alzheimer病发病有关联。

Objective：To investigate the association of genetic polymorphisms of C HRNA4, CHRNA7 with Sporadic Alzheimer＇ disease. Methods： In 23 Sporadic Alzheimer＇ disease （SAD） patients and 30 cases of normal control, exon3 of CHRNA4 was screened by PCR-DGGE and sequencing. In 16 Sporadic Alzheimer＇ disease （SAD） patients and 16 cases of normalcontrol, all exon and parts of intron of CHRNA7 were screened by PCR-DGGE and DNA sequencing. Results= CHRNA4 of three genetic polymorphisms were found in the AD and the control group= C 104T （X^2 =8.41 ,P〈0.05 ）, A 136G （X^2 =16.21 , P〈0.05）, G169A （X^2 =3.98, P〈0.05） . CHRNA7 of two genetic polymorphisms were found in the AD and the control group= G 3133418 C （X^2 =4. 571,P〉0. 05） , 117643＋ GTG inserted （X2 =1. 032,P〉0. 5） Conclusions= These three genetic polymorphisms may be associated with pathogenesis of SAD, since there is statistical difference between the AD and control group. These polymorphisms may be associated with Sporadic Alzheimer＇ disease