AUTHOR=Yan Yi , Zhao Aonan , Qui Yinghui , Li Yuanyuan , Yan Ran , Wang Ying , Xu Wei , Deng Yulei 

TITLE=Genetic Association of FERMT2, HLA-DRB1, CD2AP, and PTK2B Polymorphisms With Alzheimer’s Disease Risk in the Southern Chinese Population

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=12

YEAR=2020

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2020.00016

DOI=10.3389/fnagi.2020.00016

ISSN=1663-4365

ABSTRACT=<sec><title>Objectives</title><p>This study aimed to explore the relationship between 18 single nucleotide polymorphisms (SNPs) and Alzheimer’s disease (AD) within the southern Chinese population.</p></sec><sec><title>Methods</title><p>A total of 420 participants, consisting of 215 AD patients and 205 sex- and age-matched controls, were recruited. The SNaPshot technique and polymer chain reaction (PCR) were used to detect the 18 SNPs. Combined with the <italic>apolipoprotein E</italic> (<italic>APOE</italic>) ε4 allele and age at onset, we performed an association analysis between these SNPs and AD susceptibility. Furthermore, we analyzed SNP-associated gene expression using the expression quantitative trait loci analysis.</p></sec><sec><title>Results</title><p>Our study found that rs17125924 of <italic>FERMT2</italic> was associated with the risk of developing AD in the dominant (<italic>P</italic> = 0.022, odds ratio [OR] = 1.57, 95% confidence interval [CI]: 1.07–2.32) and overdominant (<italic>P</italic> = 0.005, OR = 1.76, 95% CI: 1.18–2.61) models. Moreover, compared with <italic>APOE</italic> ε4 non-carriers, the frequency of the G-allele at rs17125924 was significantly higher among AD patients in <italic>APOE</italic> ε4 allele carriers (<italic>P</italic> = 0.029). The rs9271058 of <italic>HLA-DRB1</italic> (dominant, overdominant, and additive models), rs9473117 of <italic>CD2AP</italic> (dominant and additive models), and rs73223431 of <italic>PTK2B</italic> (dominant, overdominant, and additive models) were associated with early onset AD (EOAD). Using the genotype-tissue expression (GTEx) and Braineac database, we found a significant association between rs9271058 genotypes and <italic>HLA-DRB1</italic> expression levels, while the CC genotype at rs9473117 and the TT genotype of rs73223431 increased <italic>CD2AP</italic> and <italic>PTK2B</italic> gene expression, respectively.</p></sec><sec><title>Conclusion</title><p>Our study identifies the G-allele at rs17125924 as a risk factor for developing AD, especially in <italic>APOE</italic> ε4 carriers. In addition, we found that rs9271058 of <italic>HLA-DRB1</italic>, rs9473117 of <italic>CD2AP</italic>, and rs73223431 of <italic>PTK2B</italic> were associated with EOAD. Further studies with larger sample sizes are needed to confirm our results.</p></sec>