Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Jul 19;24(3):584.
doi: 10.3892/etm.2022.11521. eCollection 2022 Sep.

Association of vitamin D receptor gene haplotypes with late-onset Alzheimer's disease in a Southeastern European Caucasian population

Efthimios Dimitrakis  1 , Martha-Spyridoula Katsarou  1 , Maria Lagiou  1 , Vasiliki Papastefanopoulou  2 , Demetrios A Spandidos  3 , Aristidis Tsatsakis  4 , Socratis Papageorgiou  5 , Paraskevi Moutsatsou  2 , Katerina Antoniou  6 , Christos Kroupis  2 , Nikolaos Drakoulis  1
Affiliations

Association of vitamin D receptor gene haplotypes with late-onset Alzheimer's disease in a Southeastern European Caucasian population

Efthimios Dimitrakis et al. Exp Ther Med. .

Abstract

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.

Keywords: Alzheimer's disease; haplotypes; polymorphism; single nucleotide polymorphisms; vitamin D receptor.

PubMed Disclaimer

Conflict of interest statement

DAS is the Editor-in-Chief for the journal, but had no personal involvement in the reviewing process, or any influence in terms of adjudicating on the final decision, for this article. All the other authors declare that they have no competing interests.

Similar articles

See all similar articles

Cited by

References

    1. Loginova M, Mishchenko T, Savyuk M, Guseva S, Gavrish M, Krivonosov M, Ivanchenko M, Fedotova J, Vedunova M. Double-edged sword of vitamin D3 effects on primary neuronal cultures in hypoxic states. Int J Mol Sci. 2021;22(5417) doi: 10.3390/ijms22115417. - DOI - PMC - PubMed
    1. AlJohri R, AlOkail M, Haq SH. Neuroprotective role of vitamin D in primary neuronal cortical culture. eNeurologicalSci. 2018;14:43–48. doi: 10.1016/j.ensci.2018.12.004. - DOI - PMC - PubMed
    1. Lardner AL. Vitamin D and hippocampal development-the story so far. Front Mol Neurosci. 2015;8(58) doi: 10.3389/fnmol.2015.00058. - DOI - PMC - PubMed
    1. Faye PA, Poumeaud F, Miressi F, Lia AS, Demiot C, Magy L, Favreau F, Sturtz FG. Focus on 1,25-dihydroxyvitamin D3 in the peripheral nervous system. Front Neurosci. 2019;13(348) doi: 10.3389/fnins.2019.00348. - DOI - PMC - PubMed
    1. DeLuca GC, Kimball SM, Kolasinski J, Ramagopalan SV, Ebers GC. Review: The role of vitamin D in nervous system health and disease. Neuropathol Appl Neurobiol. 2013;39:458–484. doi: 10.1111/nan.12020. - DOI - PubMed