Abstract
ObjectivesThis study aimed to explore the relationship between 18 single nucleotide polymorphisms (SNPs) and Alzheimer’s disease (AD) within the southern Chinese population.MethodsA 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 apolipoprotein E (APOE) 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.ResultsOur study found that rs17125924 of FERMT2 was associated with the risk of developing AD in the dominant (P = 0.022, odds ratio [OR] = 1.57, 95% confidence interval [CI]: 1.07–2.32) and overdominant (P = 0.005, OR = 1.76, 95% CI: 1.18–2.61) models. Moreover, compared with APOE ε4 non-carriers, the frequency of the G-allele at rs17125924 was significantly higher among AD patients in APOE ε4 allele carriers (P = 0.029). The rs9271058 of HLA-DRB1 (dominant, overdominant, and additive models), rs9473117 of CD2AP (dominant and additive models), and rs73223431 of PTK2B (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 HLA-DRB1 expression levels, while the CC genotype at rs9473117 and the TT genotype of rs73223431 increased CD2AP and PTK2B gene expression, respectively.ConclusionOur study identifies the G-allele at rs17125924 as a risk factor for developing AD, especially in APOE ε4 carriers. In addition, we found that rs9271058 of HLA-DRB1, rs9473117 of CD2AP, and rs73223431 of PTK2B were associated with EOAD. Further studies with larger sample sizes are needed to confirm our results.
Highlights
Alzheimer’s disease (AD), characterized by progressive memory loss and behavioral changes, accounts for two-thirds of dementia cases, posing a significant burden on the affected families and society (Fransquet et al, 2018)
In apolipoprotein E (APOE) ε4 carriers, the allele and genotype frequencies of FERMT2 rs17125924 were significantly different between AD patients and controls, with allele G found to be higher in the case group than in the control (Table 2)
After adjustment for age and sex, the dominant, overdominant and additive models of rs17125924 were associated with AD
Summary
Alzheimer’s disease (AD), characterized by progressive memory loss and behavioral changes, accounts for two-thirds of dementia cases, posing a significant burden on the affected families and society (Fransquet et al, 2018). Over the past few decades, genomewide association studies (GWAS), which overcome sample size limitations, were taken advantage of to study genetic changes that may contribute to AD. Meta-analyses of GWAS in populations of European ancestry have identified multiple susceptibility genes associated with AD, such as CLU, CR1, MS4A4, CD2AP, CD33, and EPHA1 (Lambert et al, 2009; Naj et al, 2011). In East Asian studies, no significant differences were observed in the genotype and estimated allele frequency distribution of single nucleotide polymorphisms (SNPs) within ABCA7, CD2AP, and EPHA1 (Tan et al, 2013), suggesting that the genetic basis for AD susceptibility may be ethnicity-specific. Our previous study found that rs3865444 of CD33 and rs610932 of MS4A6A may contribute to AD risk in the Chinese Han population, which was in line with the findings of preceding GWAS studies (Deng et al, 2012)
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