Association between Vitamin D Receptor Gene Polymorphism and Alzheimer’s Disease

Association between Vitamin D Receptor Gene Polymorphism and Alzheimer's Disease

DUYGU GEZEN-AK,¹ ERDINÇ DURSUN,¹ TURAN ERTAN,² HAMET HANAGASI,³ HAKAN GÜRVIT,³ MURAT EMRE,³ ENGIN EKER,² MELEK ÖZTÜRK,¹ FUNDA ENGIN² and SELMA YILMAZER¹

¹Istanbul University, Cerrahpasa Faculty of Medicine, Department of Medical Biology, Istanbul, Turkey
²Istanbul University, Cerrahpasa Faculty of Medicine Department of Geropsychiatry, Istanbul, Turkey
³Istanbul University, Istanbul Faculty of Medicine, Department of Neurology, Behavioral and Movement Disorders Unit, Istanbul, Turkey

Vitamin D₃ is known to be involved in neuroprotection and exert its neuroprotective effects by modulating neuronal calcium homeostasis and production of neurotrophins. The single nucleotide polymorphisms (SNP) in vitamin D receptor (VDR) gene which can influence the affinity of vitamin D₃ to its receptor may be related to neurodegenerative diseases and neuronal damage by altering the vitamin D-mediated pathways. In this study, our aim was to determine whether there is an association between VDR gene and late-onset Alzheimer's disease (AD) in order to see if vitamin D contributes to AD or not. One hundred and four cases of dementia of Alzheimer type and 109 age-matched controls were genotyped according to ApaI (a: + restriction site and A: no restriction site) and TaqI (t: + restriction site and T: no restriction site) sites in intron 8 and exon 9 of the ligand-binding site of VDR gene. When the controls and patients were compared for their ApaI genotypes, the frequency of the patients with Aa genotype was significantly higher than the frequency of the healthy individuals with the same genotype (p = 0.008, χ² = 9.577, OR = 2.30). Thus, the “Aa” genotype may increase the risk of developing AD 2.3 times when compared with the “AA” genotype. On the other hand, the “AT” haplotype was significantly higher in controls (p = 0.006) indicating a protective role of the “AT” haplotype in AD. Consequently, this study provides evidence for a possible link between AD and vitamin D.

keywords —— vitamin D; VDR; Alzheimer's disease; SNP; haplotype

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Tohoku J. Exp. Med., 2007, 212, 275-282

Correspondence: Prof. Dr. Selma Yilmazer, Department of Medical Biology, Cerrahpasa Faculty of Medicine, Istanbul University, 34812, Fatih, Istanbul, Turkey.

e-mail: selmayilmazer@mynet.com