Yanfei Ding, Haijuan Chen, Yi Yan, Yinghui Qiu, Aonan Zhao, Binyin Li, Wei Xu, Yulei Deng
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Results: Adjusted for sex and age, we found rs6572869 (FERMT2), rs11604680 (CELF1), and rs1317149 (CELF1) were associated with AD risk in the dominant (rs6572869: p = 0.022, OR = 1.55; rs11604680: p = 0.007, OR = 1.68; rs1317149: p = 0.033, OR = 1.50) and overdominant models (rs6572869: p = 0.001, OR = 1.96; rs11604680: p = 0.002, OR = 1.82; rs1317149: p = 0.003, OR = 1.80). rs9898218 (COPI) was associated with AD risk in the overdominant model (p = 0.004, OR = 1.81). Further, rs2741342 (CHRNA2) was associated with AD protection in the dominant (p = 0.002, OR = 0.5) and additive models (p = 0.002, OR = 0.64). Mutations in rs10742814 (CELF1), rs11039280 (CELF1), and rs3752242 (ABCA7) contributed to AD protection. Among them, rs10742814 (CELF1), rs3752242 (ABCA7), and rs11039280 (CELF1) were more significantly associated with AD carrying APOE ɛ4, whereas rs1317149 (CELF1) showed an opposite trend. Interestingly, rs4147912 (ABCA7) and rs2516049 (HLA-DRB1) were identified to be relevant with AD carrying APOE ɛ4. Using expression quantitative trait locus analysis, we found polymorphisms in CELF1 (rs10742814 and rs11039280), ABCA7 (rs4147912), HLA-DRB1 (rs2516049), and ADGRF4 (rs1109581) correlated with their corresponding gene expression in the brain. Conclusions: We identified four risk and four protective SNPs associated with AD in the Southern Chinese population, with different correlations between APOE ɛ4 carriers and non-carriers. rs4147912 (ABCA7) and rs2516049 (HLA-DRB1) were associated with AD carrying APOE ɛ4.","PeriodicalId":73594,"journal":{"name":"Journal of Alzheimer's disease reports","volume":" 6","pages":"0"},"PeriodicalIF":2.8000,"publicationDate":"2023-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Relationship Between FERMT2, CELF1, COPI, CHRNA2, and ABCA7 Genetic Polymorphisms and Alzheimer’s Disease Risk in the Southern Chinese Population\",\"authors\":\"Yanfei Ding, Haijuan Chen, Yi Yan, Yinghui Qiu, Aonan Zhao, Binyin Li, Wei Xu, Yulei Deng\",\"doi\":\"10.3233/adr-230072\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Background: Alzheimer’s disease (AD) is a multi-gene inherited disease, and apolipoprotein E (APOE) ɛ4 is a strong risk factor. Other genetic factors are important but limited. Objective: This study aimed to investigate the relationship between 17 single-nucleotide polymorphisms (SNPs) and AD in the Southern Chinese populations. Methods: We recruited 242 AD patients and 208 controls. The SNaPshot technique was used to detect the SNPs. Results: Adjusted for sex and age, we found rs6572869 (FERMT2), rs11604680 (CELF1), and rs1317149 (CELF1) were associated with AD risk in the dominant (rs6572869: p = 0.022, OR = 1.55; rs11604680: p = 0.007, OR = 1.68; rs1317149: p = 0.033, OR = 1.50) and overdominant models (rs6572869: p = 0.001, OR = 1.96; rs11604680: p = 0.002, OR = 1.82; rs1317149: p = 0.003, OR = 1.80). rs9898218 (COPI) was associated with AD risk in the overdominant model (p = 0.004, OR = 1.81). Further, rs2741342 (CHRNA2) was associated with AD protection in the dominant (p = 0.002, OR = 0.5) and additive models (p = 0.002, OR = 0.64). Mutations in rs10742814 (CELF1), rs11039280 (CELF1), and rs3752242 (ABCA7) contributed to AD protection. Among them, rs10742814 (CELF1), rs3752242 (ABCA7), and rs11039280 (CELF1) were more significantly associated with AD carrying APOE ɛ4, whereas rs1317149 (CELF1) showed an opposite trend. Interestingly, rs4147912 (ABCA7) and rs2516049 (HLA-DRB1) were identified to be relevant with AD carrying APOE ɛ4. Using expression quantitative trait locus analysis, we found polymorphisms in CELF1 (rs10742814 and rs11039280), ABCA7 (rs4147912), HLA-DRB1 (rs2516049), and ADGRF4 (rs1109581) correlated with their corresponding gene expression in the brain. Conclusions: We identified four risk and four protective SNPs associated with AD in the Southern Chinese population, with different correlations between APOE ɛ4 carriers and non-carriers. rs4147912 (ABCA7) and rs2516049 (HLA-DRB1) were associated with AD carrying APOE ɛ4.\",\"PeriodicalId\":73594,\"journal\":{\"name\":\"Journal of Alzheimer's disease reports\",\"volume\":\" 6\",\"pages\":\"0\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2023-11-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Alzheimer's disease reports\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.3233/adr-230072\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Alzheimer's disease reports","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3233/adr-230072","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
摘要
背景:阿尔茨海默病(Alzheimer 's disease, AD)是一种多基因遗传性疾病，载脂蛋白E (APOE) 4是一个重要的危险因素。其他遗传因素也很重要，但作用有限。目的:研究中国南方人群中17个单核苷酸多态性(snp)与AD的关系。方法:我们招募了242例AD患者和208例对照组。采用SNaPshot技术检测snp。结果:经性别和年龄调整后，我们发现rs6572869 (FERMT2)、rs11604680 (CELF1)和rs1317149 (CELF1)与显性AD风险相关(rs6572869: p = 0.022, OR = 1.55;rs11604680: p = 0.007, OR = 1.68;rs1317149: p = 0.033, OR = 1.50)和优势模型(rs6572869: p = 0.001, OR = 1.96;rs11604680: p = 0.002, OR = 1.82;rs1317149: p = 0.003, OR = 1.80)。在显性模型中，rs9898218 (COPI)与AD风险相关(p = 0.004, OR = 1.81)。此外，rs2741342 (CHRNA2)在显性模型(p = 0.002, OR = 0.5)和加性模型(p = 0.002, OR = 0.64)中与AD保护相关。rs10742814 (CELF1)、rs11039280 (CELF1)和rs3752242 (ABCA7)的突变有助于AD的保护。其中，rs10742814 (CELF1)、rs3752242 (ABCA7)和rs11039280 (CELF1)与AD携带APOE ε 4的相关性更显著，而rs1317149 (CELF1)与AD携带APOE ε 4的相关性相反。有趣的是，rs4147912 (ABCA7)和rs2516049 (HLA-DRB1)被鉴定为与携带APOE 4的AD相关。通过表达数量性状位点分析，我们发现CELF1 (rs10742814和rs11039280)、ABCA7 (rs4147912)、HLA-DRB1 (rs2516049)和ADGRF4 (rs1109581)的多态性与大脑中相应基因的表达相关。结论:我们在中国南方人群中发现了与AD相关的4个风险snp和4个保护性snp, APOE ε 4携带者和非携带者之间存在不同的相关性。rs4147912 (ABCA7)和rs2516049 (HLA-DRB1)与携带APOE 4的AD相关。
Relationship Between FERMT2, CELF1, COPI, CHRNA2, and ABCA7 Genetic Polymorphisms and Alzheimer’s Disease Risk in the Southern Chinese Population
Background: Alzheimer’s disease (AD) is a multi-gene inherited disease, and apolipoprotein E (APOE) ɛ4 is a strong risk factor. Other genetic factors are important but limited. Objective: This study aimed to investigate the relationship between 17 single-nucleotide polymorphisms (SNPs) and AD in the Southern Chinese populations. Methods: We recruited 242 AD patients and 208 controls. The SNaPshot technique was used to detect the SNPs. Results: Adjusted for sex and age, we found rs6572869 (FERMT2), rs11604680 (CELF1), and rs1317149 (CELF1) were associated with AD risk in the dominant (rs6572869: p = 0.022, OR = 1.55; rs11604680: p = 0.007, OR = 1.68; rs1317149: p = 0.033, OR = 1.50) and overdominant models (rs6572869: p = 0.001, OR = 1.96; rs11604680: p = 0.002, OR = 1.82; rs1317149: p = 0.003, OR = 1.80). rs9898218 (COPI) was associated with AD risk in the overdominant model (p = 0.004, OR = 1.81). Further, rs2741342 (CHRNA2) was associated with AD protection in the dominant (p = 0.002, OR = 0.5) and additive models (p = 0.002, OR = 0.64). Mutations in rs10742814 (CELF1), rs11039280 (CELF1), and rs3752242 (ABCA7) contributed to AD protection. Among them, rs10742814 (CELF1), rs3752242 (ABCA7), and rs11039280 (CELF1) were more significantly associated with AD carrying APOE ɛ4, whereas rs1317149 (CELF1) showed an opposite trend. Interestingly, rs4147912 (ABCA7) and rs2516049 (HLA-DRB1) were identified to be relevant with AD carrying APOE ɛ4. Using expression quantitative trait locus analysis, we found polymorphisms in CELF1 (rs10742814 and rs11039280), ABCA7 (rs4147912), HLA-DRB1 (rs2516049), and ADGRF4 (rs1109581) correlated with their corresponding gene expression in the brain. Conclusions: We identified four risk and four protective SNPs associated with AD in the Southern Chinese population, with different correlations between APOE ɛ4 carriers and non-carriers. rs4147912 (ABCA7) and rs2516049 (HLA-DRB1) were associated with AD carrying APOE ɛ4.
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