Tohoku J. Exp. Med., 2012 Nov, 228(3)

Vitamin D Receptor Gene Haplotype Is Associated with Late-Onset Alzheimer's Disease

DUYGU GEZEN-AK,¹ ERDINÇ DURSUN,¹ BASAR BILGIÇ,² HASMET HANAGASI,² TURAN ERTAN,³ HAKAN GÜRVIT,² MURAT EMRE,² ENGIN EKER,³ TURGUT ULUTIN,¹ ÖMER UYSAL⁴ and SELMA YILMAZER¹

¹Department of Medical Biology, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey
²Behavioral and Movement Disorders Unit, Department of Neurology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
³Department of Geropsychiatry, Cerrahpasa Faculty of Medicine, Istanbul University, Istanbul, Turkey
⁴Department of Biostatistics and Medical Informatics, School of Medicine, Bezmialem Vakif University, Istanbul, Turkey

Vitamin D₃ is a neurosteroid that mediates its effects via the vitamin D receptor (VDR). The VDR gene is located on chromosome 12q13 and consists of 9 exons. VDR contains the DNA-binding site encoded by exons 2 and 3 and the ligand-binding site encoded by exons 4 - 9. Our earlier study showed that the ApaI polymorphic site of the VDR gene is associated with late-onset Alzheimer's disease (AD). Here, we investigated the association between additional polymorphisms of the VDR gene and AD using the same samples. Two single nucleotide polymorphisms (SNPs) in intron 8 (BsmI and Tru9I polymorphisms) and one in exon 2 (FokI polymorphism) of the VDR gene were examined in up to 108 AD patients and 115 age-matched controls. Genotypes were determined with polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods. Haplotype analysis also included the previously studied polymorphic sites that were recognized by TaqI (in exon 9) and ApaI (in intron 8) restriction enzymes. There was no significant difference between AD patients and controls when their genotypes for BsmI, Tru9I and FokI polymorphic sites were compared. However, the frequency of “TaubF” haplotype (alleles of TaqI, ApaI, Tru9I, BsmI and FokI, respectively), which was determined by analyzing 5 polymorphisms together, was significantly higher in the AD patient group, suggesting that this haplotype is a risk factor in AD. Our results point out a possible link between AD and certain VDR polymorphisms and indicate that individuals with these polymorphisms might be vulnerable to AD.

keywords —— Alzheimer's disease; haplotype; neurodegeneration; vitamin D; vitamin D receptor

© 2012 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2012, 228, 189-196

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

e-mail: selmayilmazer@mynet.com