Xixi Liu1, Pengfei Wu2, Lu Shen1,3,4,5, Bin Jiao1,3, Xinxin Liao6, Haochen Wang7, Jiangnan Peng7, Zhangyuan Lin5,7. 1. Department of Neurology, Xiangya Hospital, Central South University, Changsha, China. 2. Hunan Provincial Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha, China. 3. Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, China. 4. National Clinical Research Center for Geriatric Diseases, Changsha, China. 5. Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, Changsha, China. 6. Department of Geriatrics Neurology, Xiangya Hospital, Central South University, Changsha, China. 7. Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, China.
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.
Background: Vitamin Dinsufficiency 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, CYP2R1rs10741657 T>C, DHCR7rs12785878 T>C, and CYP24A1rs6013897 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 ADpatients (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: DHCR7rs12785878 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 DHCR7rs12785878 T>C might be associated with an increased risk of EOAD in the Chinese population, while other polymorphisms related to vitamin Dinsufficiency might not be. However, due to the limited data in this study, replication studies in a larger sample are required.