Dataset Information

Vitamin D Receptor (VDR) Polymorphisms and Late-Onset Alzheimer's Disease: An Association Study.

ABSTRACT: BACKGROUND: Late-onset Alzheimer's disease (AD), a genetically heterogeneous neurodegenerative disorder, is the most common form of dementia in people over 65 years old. The role of vitamin D in neuropsychiatric and neurodegenerative disorders such as AD has been supported by epidemiologic investigations and animal models, as well. We examined the association of the vitamin D receptor (VDR) gene polymorphisms and late-onset AD in an Iranian population. METHODS: This study was performed in Tehran, Iran from 2007 to 2008. Totally, 145 AD patients and 162 age-matched unrelated healthy controls were included. The genotype and allele frequencies for the VDR polymorphisms, ApaI (G>T; rs7975232) and TaqI (C>T; rs731236), were determined in the case and control subjects PCR-RFLP analysis. Logistic regression analysis was performed to assess the effect of mutant genotype or allele in the study groups. RESULTS: The statistical analyses showed significant differences neither in genotype nor in allele frequencies of the ApaI and TaqI polymorphisms between the case and control groups. CONCLUSION: It seems that the ApaI and TaqI polymorphisms are not associated with the risk of late-onset AD in Iranian population.

SUBMITTER: Khorram Khorshid HR

PROVIDER: S-EPMC4499066 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Vitamin D Receptor (VDR) Polymorphisms and Late-Onset Alzheimer's Disease: An Association Study.

Khorram Khorshid Hamid Reza HR Gozalpour Elnaz E Saliminejad Kioomars K Karimloo Masood M Ohadi Mina M Kamali Koorosh K

Iranian journal of public health 20131101 11

<h4>Background</h4>Late-onset Alzheimer's disease (AD), a genetically heterogeneous neurodegenerative disorder, is the most common form of dementia in people over 65 years old. The role of vitamin D in neuropsychiatric and neurodegenerative disorders such as AD has been supported by epidemiologic investigations and animal models, as well. We examined the association of the vitamin D receptor (VDR) gene polymorphisms and late-onset AD in an Iranian population.<h4>Methods</h4>This study was perfor ...[more]

PMID: 26171337

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Project description:Vitamin D receptor (VDR) gene single nucleotide polymorphisms (SNPs) have been investigated over the past years with the aim of identifying any association with the development of Alzheimer's disease (AD). However, information regarding the potential association of VDR SNP haplotypes with AD is limited. The aim of the present study was to provide additional knowledge on the effects of VDR haplotypes on the development of late-onset AD in a cohort of Southeastern European Caucasians (SECs). The study sample included 78 patients with late-onset AD and 103 healthy subjects as the control group. VDR SNPs that were analyzed were TaqI (rs731236), BsmI (rs1544410) and FokI (rs2228570). The CAC (TaqI, BsmI and FokI) haplotype was found to be associated with a 53% lower risk of developing the disease (OR, 0.47; 95% CI, 0.23-0.96; P=0.04) and the TAC (TaqI, BsmI and FokI) haplotype was associated with an ~6-fold greater risk of developing AD (OR, 6.19; 95% CI, 1.91-20.13; P=0.0028). Female subjects carrying the TAC haplotype had a ~9-fold greater risk of developing AD in comparison to female control subjects (OR, 9.27; 95% CI, 1.86-46.28; P<0.05). The TaqI and BsmI polymorphisms were in high linkage disequilibrium (D'=0.9717, r=0.8467) and produced a haplotype with a statistically significant different frequency between the control and AD group. The TA (TaqI and BsmI) haplotype was associated with an ~8-fold greater risk of developing AD (OR, 8.27; 95% CI, 2.70-25.28; P<0.05). Female TA carriers had an ~14-fold greater risk of developing the disease in comparison to female control subjects (OR, 13.93; 95% CI, 2.95-65.87; P<0.05). On the whole, the present study demonstrates that in the SEC population, TAC and TA are risk haplotypes for AD, while the CAC haplotype may act protectively. SEC women carrying the TAC or TA haplotype are at a greater risk of developing AD, thus suggesting that women are markedly affected by the poor utilization of vitamin D induced by the VDR haplotype.

Project description:Late-onset Alzheimer's disease (LOAD) is an age related neurodegenerative disease with a high prevalence that places major demands on healthcare resources in societies with increasingly aged populations. The only extensively replicable genetic risk factor for LOAD is the apolipoprotein E gene. In order to identify additional genetic risk loci we have conducted a genome-wide association (GWA) study in a large LOAD case - control sample, reducing costs through the use of DNA pooling.DNA samples were collected from 1,082 individuals with LOAD and 1,239 control subjects. Age at onset ranged from 60 to 95 and Controls were matched for age (mean = 76.53 years, SD = 33), gender and ethnicity. Equimolar amounts of each DNA sample were added to either a case or control pool. The pools were genotyped using Illumina HumanHap300 and Illumina Sentrix HumanHap240S arrays testing 561,494 SNPs. 114 of our best hit SNPs from the pooling data were identified and then individually genotyped in the case - control sample used to construct the pools.Highly significant association with LOAD was observed at the APOE locus confirming the validity of the pooled genotyping approach.For 109 SNPs outside the APOE locus, we obtained uncorrected p-values </= 0.05 for 74 after individual genotyping. To further test these associations, we added control data from 1400 subjects from the 1958 Birth Cohort with the evidence for association increasing to 3.4 x 10-6 for our strongest finding, rs727153.rs727153 lies 13 kb from the start of transcription of lecithin retinol acyltransferase (phosphatidylcholine - retinol O-acyltransferase, LRAT). Five of seven tag SNPs chosen to cover LRAT showed significant association with LOAD with a SNP in intron 2 of LRAT, showing greatest evidence of association (rs201825, p-value = 6.1 x 10-7).We have validated the pooling method for GWA studies by both identifying the APOE locus and by observing a strong enrichment for significantly associated SNPs. We provide evidence for LRAT as a novel candidate gene for LOAD. LRAT plays a prominent role in the Vitamin A cascade, a system that has been previously implicated in LOAD.

Dataset Information

Vitamin D Receptor (VDR) Polymorphisms and Late-Onset Alzheimer's Disease: An Association Study.

Publications

Vitamin D Receptor (VDR) Polymorphisms and Late-Onset Alzheimer's Disease: An Association Study.

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