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Apa I, Taq I and Fok I VDR polymorphisms: Functional effect on mRNA levels of amyloid beta transporters LRP1 and P‐gp in lymphocytes of mild cognitive impairment patients
Author(s) -
Arevalo Nohela,
Castillo Daniela,
Rogers Nicole,
Delgado Carolina,
Farías Gonzalo,
Behrens María Isabel,
SanMartín Carol D.
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.045564
Subject(s) - calcitriol receptor , single nucleotide polymorphism , allele , medicine , genotyping , genotype , microbiology and biotechnology , endocrinology , vitamin d and neurology , biology , genetics , gene
Abstract Background LRP1 and P‐gp are the major efflux transporters of β‐amyloid peptide (Aβ) across the blood brain barrier and the expression of both transporters is mediated by the vitamin D receptor (VDR). Three single nucleotide VDR polymorphisms (SNPs) Taq I, Apa I and Fok I have been related to mild cognitive impairment (MCI); however, their functional effect on the expression of VDR and its target genes remains unclear. Method 76 MCI patients and 133 elderly volunteers were cognitively screened with the Montreal Cognitive assessment (MoCA) and MoCA‐MIS after signing an informed consent approved by the Ethics Committee of Hospital Clínico Unversidad de Chile. The VDR SNPs Apa (rs7975232), Taq (rs731236) and Fok I (rs2228570) were determined by TaqMan SNP genotyping assay. mRNA levels of VDR , LRP1 and P‐gp were evaluated by qPCR. Result The C and T alleles of Apa I and Taq I respectively were more frequent in the MCI (p < 0.05); additionally the odds ratio analysis (OR) was significant for both alleles (C allele OR: 1.5 p = 0.049; T allele OR: 1.89, p = 0.0044). There were no significant differences for Fok I polymorphism between the groups. Furthermore, the homozygous CC of Apa I had significantly lower mRNA levels of P‐gp and VDR than the homozygous AA and heterozygous AC (p < 0.05). The carriers of one copy of the C allele (TC) of Fok I had lower mRNA levels of VDR and of both transporters than the homozygous TT (p < 0.005). Conclusion The C and T alleles of Apa I and Taq I respectively might be risk alleles for MCI, as reported in other populations. In addition, we found that SNPs of the VDR gene are related to the decrease of the mRNA levels of the Aβ transporter P‐gp and the transcription factor VDR.