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

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 Apal 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 (Bsml and Tru9l polymorphisms) and one in exon 2 (Fokl 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 Taql (in exon 9) and Apal (in intron 8) restriction enzymes. There was no significant difference between AD patients and controls when their genotypes for Bsml, Tru9l and Fokl polymorphic sites were compared. However, the frequency of "TaubF" haplotype (alleles of Taql, Apal, Tru9l, Bsml and Fokl, 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. [ABSTRACT FROM AUTHOR]