Abstract
Background: Vitamin D insufficiency has been considered a risk factor for Alzheimer's disease (AD) in several studies. Recently, four single-nucleotide polymorphisms (SNPs) to be genome-wide significant for 25-hydroxyvitamin D [25(OH)D] were identified to have an association with the risk of AD. These include GC rs2282679 A>C, CYP2R1 rs10741657 T>C, DHCR7 rs12785878 T>C, and CYP24A1 rs6013897 T>A. However, the association between these polymorphisms and AD susceptibility in the Chinese population remains unclear.Methods: A case-control cohort study was conducted in 676 AD patients (mean age at onset was 69.52 ± 10.90 years, male: 39.2%) and 551 healthy controls (mean age was 67.73 ± 6.02 years, male: 44.8%). Genotyping was determined by PCR and SNaPshot sequencing. To determine whether the four SNPs account for risks in AD in Chinese population, multivariate logistic regression models were performed. Stratified analysis was performed based on gender and age of onset of AD, separately. Statistical significance was set at 0.0125 (0.05/4) based on Bonferroni correction.Findings: DHCR7 rs12785878 T>C was found to be significantly associated with an increased risk of early-onset Alzheimer's disease (EOAD) (n = 300, risk allele C, adjusted OR = 1.542, adjusted 95% CI = 1.176–2.023, p = 0.002). There was no statistical significance of the other three SNPs between the two groups.Interpretation: Our results suggested that DHCR7 rs12785878 T>C might be associated with an increased risk of EOAD in the Chinese population, while other polymorphisms related to vitamin D insufficiency might not be. However, due to the limited data in this study, replication studies in a larger sample are required.
Highlights
Vitamin D, a steroid hormone, is crucial for maintaining musculoskeletal health and mineral metabolism
We found DHCR7 rs12785878 T>C to be significantly associated with an increased risk of Early-onset Alzheimer’s disease (EOAD) (p = 0.002, odds ratio (OR) = 1.544, 95% confidence interval (CI) = 1.177–2.025) (Table 4), and after being adjusted for sex, the difference was still significant (p = 0.002, adjusted OR = 1.542, adjusted 95% CI = 1.176–2.023)
We investigated the association of single-nucleotide polymorphisms (SNPs) related to vitamin D insufficiency and the risk of Alzheimer’s disease (AD) in a cohort of Chinese subjects with AD and healthy controls
Summary
Vitamin D, a steroid hormone, is crucial for maintaining musculoskeletal health and mineral metabolism. Large-scale cohort studies and cross-sectional studies suggested that a decreased 25-hydroxyvitamin D [25(OH)D] level is associated with an increased risk of Alzheimer’s disease (AD) (Balion et al, 2012; Afzal et al, 2014; Littlejohns et al, 2014). Vitamin D insufficiency has been considered a risk factor for Alzheimer’s disease (AD) in several studies. Four single-nucleotide polymorphisms (SNPs) to be genome-wide significant for 25-hydroxyvitamin D [25(OH)D] were identified to have an association with the risk of AD. These include GC rs2282679 A>C, CYP2R1 rs10741657 T>C, DHCR7 rs12785878 T>C, and CYP24A1 rs6013897 T>A. The association between these polymorphisms and AD susceptibility in the Chinese population remains unclear
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