Vitamin D Receptor and Megalin Gene Polymorphisms Are Associated with Longitudinal Cognitive Change Among African-American Urban Adults

Overview

Journal J Nutr

Publisher Elsevier

Specialty Nutritional Sciences

Date 2017 Apr 28

PMID 28446629

Citations 6

Authors

May A Beydoun

Salman M Tajuddin

Greg A Dore

Jose-Atilio Canas

Hind A Beydoun

Michele K Evans

Alan B Zonderman

Affiliations

Soon will be listed here.

Abstract

The link between longitudinal cognitive change and polymorphisms in the vitamin D receptor () and [or LDL receptor-related protein 2 ()] genes remains unclear, particularly among African-American (AA) adults. We aimed to evaluate associations of single nucleotide polymorphisms (SNPs) for [rs11568820 (Cdx-2:T/C), rs1544410 (BsmI:G/A), rs7975232 (ApaI:A/C), rs731236 (TaqI:G/A)] and [rs3755166:G/A,rs2075252:C/T, rs2228171:C/T] genes with longitudinal cognitive performance change in various domains of cognition. Data from 1024 AA urban adult participants in the Healthy Aging in Neighborhoods of Diversity Across the Life Span (Baltimore, Maryland) with complete genetic data were used, of whom 660-797 had complete data on 9 cognitive test scores at baseline and/or the first follow-up examination and complete covariate data (∼52% female; mean age: ∼52 y; mean years of education: 12.6 y). Time between examination visits 1 (2004-2009) and 2 (2009-2013) ranged from <1 y to ∼8 y, with a mean ± SD of 4.64 ± 0.93 y. Latent class and haplotype analyses were conducted by creating gene polymorphism groups that were related to longitudinal annual rate of cognitive change predicted from mixed-effects regression models. Among key findings, the rs3755166:G/A SNP was associated with faster decline on the Mini-Mental State Examination overall (β = -0.002, = 0.018) and among women. (BsmI/ApaI/TaqI: G-/A-/A-) SNP latent class [SNPLC; compared with (ApaI: "AA")] was linked to faster decline on the Verbal Fluency Test, Categorical, in women, among whom the (rs2228171: "TT") SNPLC (compared with :rs2228171: "CC") was also associated with a faster decline on the Trailmaking Test, Part B (Trails B), but with a slower decline on the Digit Span Backward (DS-B). Moreover, among men, the SNP haplotype (SNPHAP; GCA:baT) was associated with a slower decline on the Trails B, whereas the SNPHAP (GCC) was associated with a faster decline on the DS-B, reflected as a faster decline on cognitive domain 2 ("visual/working memory"). and gene variations can alter age-related cognitive trajectories differentially between men and women among AA urban adults, specifically in global mental status and domains of verbal fluency, visual/working memory, and executive function.

Citing Articles

Maternal Vit D supplementation in AMA mice and the role of Vit D/VDR signaling in the offspring's cognition.

Li D, Xu Y, Wang K, Yang Z, Li H, Lei S Am J Transl Res. 2021; 13(11):12650-12661.

PMID: 34956480 PMC: 8661169.

Neuronal megalin mediates synaptic plasticity-a novel mechanism underlying intellectual disabilities in megalin gene pathologies.

Gomes J, Lobo A, Nogueira R, Terceiro A, Costelha S, Lopes I Brain Commun. 2020; 2(2):fcaa135.

PMID: 33225275 PMC: 7667529. DOI: 10.1093/braincomms/fcaa135.

Hepatocyte gene expression and DNA methylation as ancestry-dependent mechanisms in African Americans.

Park C, De T, Xu Y, Zhong Y, Smithberger E, Alarcon C NPJ Genom Med. 2019; 4:29.

PMID: 31798965 PMC: 6877651. DOI: 10.1038/s41525-019-0102-y.

Amyloid Beta 1-42 Alters the Expression of miRNAs in Cortical Neurons.

Dursun E, Candas E, Yilmazer S, Gezen-Ak D J Mol Neurosci. 2018; 67(2):181-192.

PMID: 30515701 DOI: 10.1007/s12031-018-1223-y.

Vitamin D Metabolism-Related Gene Haplotypes and Their Association with Metabolic Disturbances Among African-American Urban Adults.

Beydoun M, Hossain S, Tajuddin S, Canas J, Kuczmarski M, Beydoun H Sci Rep. 2018; 8(1):8035.

PMID: 29795187 PMC: 5966433. DOI: 10.1038/s41598-018-26230-w.

References

Hammad S, Ranganathan S, Loukinova E, Twal W, Argraves W . Interaction of apolipoprotein J-amyloid beta-peptide complex with low density lipoprotein receptor-related protein-2/megalin. A mechanism to prevent pathological accumulation of amyloid beta-peptide. J Biol Chem. 1997; 272(30):18644-9. DOI: 10.1074/jbc.272.30.18644. View

Eyles D, Burne T, McGrath J . Vitamin D, effects on brain development, adult brain function and the links between low levels of vitamin D and neuropsychiatric disease. Front Neuroendocrinol. 2012; 34(1):47-64. DOI: 10.1016/j.yfrne.2012.07.001. View

Wigginton J, Cutler D, Abecasis G . A note on exact tests of Hardy-Weinberg equilibrium. Am J Hum Genet. 2005; 76(5):887-93. PMC: 1199378. DOI: 10.1086/429864. View

Kuningas M, Mooijaart S, Jolles J, Slagboom P, Westendorp R, van Heemst D . VDR gene variants associate with cognitive function and depressive symptoms in old age. Neurobiol Aging. 2007; 30(3):466-73. DOI: 10.1016/j.neurobiolaging.2007.07.001. View

Beydoun M, Boueiz A, Abougergi M, Kitner-Triolo M, Beydoun H, Resnick S . Sex differences in the association of the apolipoprotein E epsilon 4 allele with incidence of dementia, cognitive impairment, and decline. Neurobiol Aging. 2010; 33(4):720-731.e4. PMC: 2974952. DOI: 10.1016/j.neurobiolaging.2010.05.017. View

Nykjaer A, Dragun D, Walther D, Vorum H, Jacobsen C, Herz J . An endocytic pathway essential for renal uptake and activation of the steroid 25-(OH) vitamin D3. Cell. 1999; 96(4):507-15. DOI: 10.1016/s0092-8674(00)80655-8. View

Durk M, Han K, Chow E, Ahrens R, Henderson J, Fraser P . 1α,25-Dihydroxyvitamin D3 reduces cerebral amyloid-β accumulation and improves cognition in mouse models of Alzheimer's disease. J Neurosci. 2014; 34(21):7091-101. PMC: 6608194. DOI: 10.1523/JNEUROSCI.2711-13.2014. View

Dietrich M, Spuch C, Antequera D, Rodal I, de Yebenes J, Molina J . Megalin mediates the transport of leptin across the blood-CSF barrier. Neurobiol Aging. 2007; 29(6):902-12. DOI: 10.1016/j.neurobiolaging.2007.01.008. View

Zlokovic B, Martel C, Matsubara E, McComb J, Zheng G, McCluskey R . Glycoprotein 330/megalin: probable role in receptor-mediated transport of apolipoprotein J alone and in a complex with Alzheimer disease amyloid beta at the blood-brain and blood-cerebrospinal fluid barriers. Proc Natl Acad Sci U S A. 1996; 93(9):4229-34. PMC: 39517. DOI: 10.1073/pnas.93.9.4229. View

10.

Hammes A, Andreassen T, Spoelgen R, Raila J, Hubner N, Schulz H . Role of endocytosis in cellular uptake of sex steroids. Cell. 2005; 122(5):751-62. DOI: 10.1016/j.cell.2005.06.032. View

11.

Cedazo-Minguez A . Apolipoprotein E and Alzheimer's disease: molecular mechanisms and therapeutic opportunities. J Cell Mol Med. 2008; 11(6):1227-38. PMC: 4401287. DOI: 10.1111/j.1582-4934.2007.00130.x. View

12.

Deane R, Wu Z, Sagare A, Davis J, Yan S, Hamm K . LRP/amyloid beta-peptide interaction mediates differential brain efflux of Abeta isoforms. Neuron. 2004; 43(3):333-44. DOI: 10.1016/j.neuron.2004.07.017. View

13.

Varzaneh F, Sharifi F, Hossein-Nezhad A, Mirarefin M, Maghbooli Z, Ghaderpanahi M . Association of vitamin D receptor with longevity and healthy aging. Acta Med Iran. 2013; 51(4):236-41. View

14.

Keyimu K, Zhou X, Miao H, Zou T . Relationship between vitamin D receptor gene polymorphism and mild cognitive impairment in elderly Uygur people. Int J Clin Exp Med. 2015; 7(12):5282-8. PMC: 4307479. View

15.

Roher A, Lowenson J, Clarke S, Woods A, Cotter R, Gowing E . beta-Amyloid-(1-42) is a major component of cerebrovascular amyloid deposits: implications for the pathology of Alzheimer disease. Proc Natl Acad Sci U S A. 1993; 90(22):10836-40. PMC: 47873. DOI: 10.1073/pnas.90.22.10836. View

16.

Przybelski R, Binkley N . Is vitamin D important for preserving cognition? A positive correlation of serum 25-hydroxyvitamin D concentration with cognitive function. Arch Biochem Biophys. 2007; 460(2):202-5. DOI: 10.1016/j.abb.2006.12.018. View

17.

Carro E, Spuch C, Trejo J, Antequera D, Torres-Aleman I . Choroid plexus megalin is involved in neuroprotection by serum insulin-like growth factor I. J Neurosci. 2005; 25(47):10884-93. PMC: 6725866. DOI: 10.1523/JNEUROSCI.2909-05.2005. View

18.

Jorde R, Mathiesen E, Rogne S, Wilsgaard T, Kjaergaard M, Grimnes G . Vitamin D and cognitive function: The Tromsø Study. J Neurol Sci. 2015; 355(1-2):155-61. DOI: 10.1016/j.jns.2015.06.009. View

19.

Laczmanski L, Jakubik M, Bednarek-Tupikowska G, Rymaszewska J, Sloka N, Lwow F . Vitamin D receptor gene polymorphisms in Alzheimer's disease patients. Exp Gerontol. 2015; 69:142-7. DOI: 10.1016/j.exger.2015.06.012. View

20.

Wang L, Pan X, Wang Y, Tang H, Deng Y, Ren R . A single nucleotide polymorphism in LRP2 is associated with susceptibility to Alzheimer's disease in the Chinese population. Clin Chim Acta. 2010; 412(3-4):268-70. DOI: 10.1016/j.cca.2010.10.015. View