AUTHOR=Xu Lingjia , Chen Yanxing , Shen Ting , Lin Caixiu , Zhang Baorong 

TITLE=Genetic Analysis of PICK1 Gene in Alzheimer's Disease: A Study for Finding a New Gene Target

JOURNAL=Frontiers in Neurology

VOLUME=9

YEAR=2019

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2018.01169

DOI=10.3389/fneur.2018.01169

ISSN=1664-2295

ABSTRACT=<p><bold>Background:</bold> 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. <italic>PICK1</italic> gene polymorphisms have been identified in psychological and other related disorders.</p><p><bold>Methods:</bold> This study included 133 sporadic AD patients and 173 healthy controls. All coding exons and intron-exon boundaries of the <italic>PICK1</italic> gene were amplified by polymerase chain reaction (PCR), which were subsequently sequenced and analyzed.</p><p><bold>Results:</bold> This is the first genetic association study to investigate the association between <italic>PICK1</italic> 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 (<italic>p</italic> = 0.002; OR, 0.083; 95%CI, 0.011–0.634) and TT/TC genotypes (<italic>p</italic> = 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 (<italic>p</italic> = 0.018) in <italic>APOE</italic>ε4 allele carriers, while the frequency of the T allele of rs149474436 was significantly lower among AD patients in <italic>APOE</italic>ε4 non-carriers (<italic>p</italic> = 0.005).</p><p><bold>Conclusions:</bold> Our results suggest that <italic>PICK1</italic> 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.</p>