Xu Lingjia, Chen Yanxing, Shen Ting, Lin Caixiu, Zhang Baorong
Department of Neurology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Department of Neurology, The Second Hospital of Shaoxing, Shaoxing, China.
Front Neurol. 2019 Jan 9;9:1169. doi: 10.3389/fneur.2018.01169. eCollection 2018.
Alzheimer's disease (AD) is a neurodegenerative disease with no effective treatment. Researchers have focused on exploring biomarkers for its early diagnosis, especially on finding a new gene target. Recent studies have shown that protein interacting with C-kinase-1(PICK1) is related to AD through regulating hippocampal synaptic plasticity. gene polymorphisms have been identified in psychological and other related disorders. This study included 133 sporadic AD patients and 173 healthy controls. All coding exons and intron-exon boundaries of the gene were amplified by polymerase chain reaction (PCR), which were subsequently sequenced and analyzed. This is the first genetic association study to investigate the association between gene and AD risk in Chinese Han population. Seven single nucleotide polymorphisms (SNPs) were found in our research (rs397780637, rs713729, rs2076369, rs58230476, rs7289911, rs149474436; and rs146770324 for patient M1659 only). Frequencies of the T allele ( = 0.002; OR, 0.083; 95%CI, 0.011-0.634) and TT/TC genotypes ( = 0.001) of rs149474436 were lower in AD patients than in the controls. The GG homozygotes of rs397780637 were found to be associated with an increased risk of AD ( = 0.018) in ε4 allele carriers, while the frequency of the T allele of rs149474436 was significantly lower among AD patients in ε4 non-carriers ( = 0.005). Our results suggest that gene SNPs are associated with AD susceptibility in East Asian population, T allele of rs149474436 may play as a protective factor while the rs397780637 GG homozygotes may be associated with an increased risk of AD. Further studies should be considered in a larger cohort of patients with diverse demographics.
阿尔茨海默病(AD)是一种尚无有效治疗方法的神经退行性疾病。研究人员一直专注于探索其早期诊断的生物标志物,尤其是寻找新的基因靶点。最近的研究表明,与C激酶1相互作用的蛋白(PICK1)通过调节海马突触可塑性与AD相关。在心理及其他相关疾病中已鉴定出该基因的多态性。本研究纳入了133例散发性AD患者和173例健康对照。通过聚合酶链反应(PCR)扩增该基因的所有编码外显子和内含子 - 外显子边界,随后进行测序和分析。这是首次在中国汉族人群中研究该基因与AD风险之间关联的基因关联研究。我们的研究中发现了7个单核苷酸多态性(SNP)(rs397780637、rs713729、rs2076369、rs58230476、rs7289911、rs149474436;仅患者M1659有rs146770324)。rs149474436的T等位基因(P = 0.002;OR,0.083;95%CI,0.011 - 0.634)和TT/TC基因型(P = 0.001)在AD患者中的频率低于对照组。发现rs397780637的GG纯合子与ε4等位基因携带者患AD的风险增加相关(P = 0.018),而在ε4非携带者的AD患者中,rs149474436的T等位基因频率显著更低(P = 0.005)。我们的结果表明,该基因的SNP与东亚人群的AD易感性相关,rs149474436的T等位基因可能起保护作用,而rs397780637的GG纯合子可能与AD风险增加相关。应考虑在更大的具有不同人口统计学特征的患者队列中进行进一步研究。