司君增　王秀芹　杨艳红　邢晓玲　郑立峰　亓勤德　朱峻岭

[关键词] ADAM10;基因多态性;阿尔茨海默病;整合素

[中图分类号] R749.1          [文献标识码] A          [文章编号] 1673-9701（2021）17-0001-03

Study on correlation between ADAM10 gene polymorphism and Alzheimer′s disease

SI Junzeng   WANG Xiuqin   YANG Yanhong   XING Xiaoling   ZHENG Lifeng   QI Qinde   ZHU Junling

Department of Neurology， Ji′nan City People′s Hospital， Ji′nan People′s Hospital Affiliated to Shandong First Medical University， Ji′nan 271199， China

[Abstract] Objective To explore the correlation between a disintegrin and metalloproteinase 10 gene （ADAM10） rs2305421 and rs653765 polymorphisms and the genetic susceptibility of northern Chinese Han population to Alzheimer′s disease （AD）. Methods A total of 96 AD patients （the case group） and 102 healthy people （the control group） admitted to our hospital from January 2013 to May 2020 were matched in age and gender. The ADAM10 rs2305421 and rs653765 loci were genotyped by polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP）. The distribution of genotype frequency and allele frequency between the case group and the control group was compared by chi-square test. The intensity analysis of single gene nucleotide polymorphism and AD risk was expressed by odds ratio （OR） and 95% confidence interval （95%CI）. Results The genotype of ADAM10 rs2305421 locus in the case group was [46（47.92）%]， which was higher than that in the control group [（45 （44.12）%]， with no significant difference（P>0.05）. The allele frequency of ADAM10 rs2305421 in the case group was（62.50%）， which was higher/lower than that in the control group（72.06%）， with no significant difference（P>0.05）. However， the frequency of AA genotype at ADAM10 rs653765 locus was significantly different from that of the control group（P=0.042）， and the risk of AD was increased compared with GG genotype（OR=2.99， 95%CI： 1.04-8.59）. In addition， the proportion of allele A in AD patients was significantly higher than that in the control group（OR=1.55， 95%CI： 1.01-2.36， P=0.043）. Conclusion The polymorphism of rs653765 locus of ADAM10 gene may be related to AD in Han nationality in northern China， but it has nothing to do with rs2305421 locus.

[Key words] ADAM10; Gene polymorphism; Alzheimer′s disease; Integrin

阿爾茨海默病（Alzheimer′s disease，AD）是以进行性记忆力减退和认知功能障碍为主的神经退行性疾病，是痴呆最常见的类型，约占痴呆总数的60%～80%[1-2]。整合素和金属蛋白酶（A disintegrin and metalloproteinase with thrombospondin motifs，ADAMs）是一种结合细胞膜的糖蛋白，其参与细胞信号转导、细胞粘附、细胞外基质的降解。研究表明，ADAMs参与了细胞的增殖、分化及细胞外基质的重建、血管生成、细胞迁移，涉及炎症等疾病的病理过程[3]。ADAM10的表达可以通过启动子区域的多态性调节，这已被证实同AD、行为障碍和其他疾病相关[4]。因此，本研究分析两种单核苷酸多态性（Single nucleotide polymorphisms，SNPs）即rs2305421，rs653765同AD的发病敏感性之间的相关性预测，现报道如下。

1 资料与方法

1.1 一般资料

本研究采用病例对照设计。所有受试者均无血缘关系，本研究经济南市人民医院医学伦理委员会批准。按照国家伦理标准，对所有受试者进行样本采集，并签署知情同意书。阿尔茨海默病诊断参照NINCDS-ADRDA诊断标准[3]，96例AD患者为2013年1月至2020年5月在济南市人民医院神经内科门诊及住院患者，包括男36例，女60例，年龄43～86岁，平均（66.48±3.11）岁。结合家族史及相应的临床检查，排除糖尿病、严重精神疾病、肿瘤等内科疾病。同时，102例对照组为门诊健康体检者，其中男35例，女67例，平均年龄（67.31±9.47）岁。

1.2 血液标本采集及基因组DNA提取

早晨空腹采集外周静脉血2 mL，收集后保存在EDTA抗凝的离心管。48 h内通过北京天根生化提供的DNA提取试剂盒提取基因组DNA，-80℃保存。