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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.

DHCR7 rs12785878 T>C Polymorphism Is Associated With an Increased Risk of Early Onset of Alzheimer's Disease in Chinese Population