Association of vitamin D receptor gene polymorphisms and Parkinson's disease in Hungarians

Abstract

Vitamin D receptor (VDR) gene encodes a transcription factor that influences calcium homeostasis and immunoregulation, and may play a role in neurological disorders including Parkinson's disease (PD). The investigations of the association between VDR and PD in different populations revealed various results. In a present study 100 PD patients and 109 healthy controls from the Hungarian population were genotyped for four polymorphic sites (BsmI, ApaI, FokI and TaqI) in the VDR gene. The polymorphisms were determined by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Our results demonstrate an association between the FokI C allele and PD; the frequency of the C allele was significantly higher in PD patients than in controls, suggesting that this polymorphism may have a role in the development of PD in these patients.

Vitamin D receptor gene polymorphisms and Parkinson's disease in a population with high ultraviolet radiation exposure

“…Even with an exposure range of 4200-5350 Wh/m 2 from all addresses, we did not have sufficient variability to test gene-environment interactions, as all participants were highly exposed, and we lacked a “low” UVR exposure sub-group. Participants with the lowest lifetime exposure to UVR in our study (i.e., 4200 Wh/m 2 ) were still exposed at levels higher than populations in several studies[14-16]. As such, observed gene effects reflect the relationship between VDR polymorphisms and PD in the context of lifelong high UV exposure.…”

“…Differences in findings for VDR SNPs between studies could be due to background levels of UVR exposure in the population studied. While there was not complete overlap in the polymorphisms examined, generally existing studies that included populations with very low UVR exposure [15, 16, 38], did not detect PD associations in the VDR SNPs in which we did identify associations. This could be further investigated by studying the impact of VDR genetic variation on PD in other very high or very low UVR exposed populations.…”

“…Haplotypes in the VDR that include the BsmI locus were associated with varying mRNA expression levels[12]. In Hungarian and Chinese case-control studies, CC+TC genotypes of FokI (SNP rs10735810 tagged the FokI restriction site) were more common than the TT genotype in PD patients[14, 16]. Other case-control studies of these RLFPs and other VDR polymorphisms including both smaller and larger numbers of cases did not find associations[15, 39, 40].…”

“…A small study of Korean PD patients found that the Bsm I bb genotype was significantly more common in patients than controls, a result that has not been confirmed by three subsequent case-control studies[14-16]. Genotypes containing the major allele of Fok I, a known functional VDR polymorphism, have been associated with a greater than two-fold increase in PD[14, 16]. However, in a genome-wide association study (GWAS), none of eighteen VDR SNPs examined were associated with PD risk[17].…”

“…Several epidemiologic studies of PD investigating genetic variability in the VDR have largely focused on four common VDR polymorphisms, and findings for these and other VDR polymorphisms have been generally inconsistent. A small study of Korean PD patients found that the Bsm I bb genotype was significantly more common in patients than controls, a result that has not been confirmed by three subsequent case-control studies[14-16]. Genotypes containing the major allele of Fok I, a known functional VDR polymorphism, have been associated with a greater than two-fold increase in PD[14, 16].…”