Vitamin D Receptor and Megalin Gene Polymorphisms and Their Associations with Longitudinal Cognitive Change in US Adults

Overview

Journal Am J Clin Nutr

Publisher Elsevier

Specialty Nutritional Sciences

Date 2011 Dec 16

PMID 22170372

Citations 25

Authors

May A Beydoun

Eric L Ding

Hind A Beydoun

Toshiko Tanaka

Luigi Ferrucci

Alan B Zonderman

Affiliations

Soon will be listed here.

Abstract

Background: Vitamin D receptor (VDR) and the megalin gene polymorphism's link with longitudinal cognitive change remains unclear.

Objective: The associations of single nucleotide polymorphisms (SNPs) for VDR [rs11568820 (CdX-2:T/C), rs1544410 (BsmI:G/A), rs7975232 (ApaI:A/C), rs731236 (TaqI:G/A)], and Megalin (rs3755166:G/A; rs2075252:C/T; rs4668123:C/T) genes with longitudinal cognitive performance changes were examined.

Design: Data from 702 non-Hispanic white participants in the Baltimore Longitudinal Study of Aging were used. Longitudinal annual rates of cognitive change (LARCCs) between age 50 y and the individual mean follow-up age were predicted with linear mixed models by using all cognitive score time points (prediction I) or time points before dementia onset (prediction II). Latent class, haplotype, and ordinary least squares (OLS) regression analyses were conducted.

Results: Among key findings, in OLS models with SNP latent classes as predictors for LARCCs, Megalin(2) [rs3755166(-)/rs2075252(TT)/rs4668123(T-)] compared with Megalin(1) [rs3755166(-)/rs2075252(CC)/rs4668123(-)] was associated with greater decline among men for verbal memory (prediction II). Significant sex differences were also found for SNP haplotype (SNPHAP). In women, VDR(1) [BsmI(G-)/ApaI(C-)/TaqI(A-); baT] was linked to a greater decline in category fluency (prediction I: β = -0.031, P = 0.012). The Megalin(1) SNPHAP (GCC) was related to greater decline among women for verbal memory, immediate recall [California Verbal Learning Test (CVLT), List A; prediction II: β = -0.043, P = 0.006) but to slower decline among men for delayed recall (CVLT-DR: β > 0, P < 0.0125; both predictions). In women, the Megalin(2) SNPHAP (ACC) was associated with slower decline in category fluency (prediction II: β = +0.026, P = 0.005). Another finding was that Megalin SNP rs3755166:G/A was associated with greater decline in global cognition in both sexes combined and in verbal memory in men.

Conclusion: Sex-specific VDR and Megalin gene variations can modify age-related cognitive decline among US adults.

Citing Articles

Role of Calcitriol and Vitamin D Receptor () Gene Polymorphisms in Alzheimer's Disease.

Jeong S, Sharma N, An S Int J Mol Sci. 2024; 25(9).

PMID: 38732025 PMC: 11084202. DOI: 10.3390/ijms25094806.

Role of Vitamin D Deficiency in the Pathogenesis of Cardiovascular and Cerebrovascular Diseases.

Pal E, Ungvari Z, Benyo Z, Varbiro S Nutrients. 2023; 15(2).

PMID: 36678205 PMC: 9864832. DOI: 10.3390/nu15020334.

The Efficacy of Vitamin D Supplementation in Patients With Alzheimer's Disease in Preventing Cognitive Decline: A Systematic Review.

Chakkera M, Ravi N, Ramaraju R, Vats A, Nair A, Bandhu A Cureus. 2022; 14(11):e31710.

PMID: 36569670 PMC: 9771092. DOI: 10.7759/cureus.31710.

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

Dimitrakis E, Katsarou M, Lagiou M, Papastefanopoulou V, Spandidos D, Tsatsakis A Exp Ther Med. 2022; 24(3):584.

PMID: 35949319 PMC: 9353461. DOI: 10.3892/etm.2022.11521.

Role of Neural Stem Cells and Vitamin D Receptor (VDR)-Mediated Cellular Signaling in the Mitigation of Neurological Diseases.

Uthaiah C, Beeraka N, Rajalakshmi R, Ramya C, Madhunapantula S Mol Neurobiol. 2022; 59(7):4065-4105.

PMID: 35476289 DOI: 10.1007/s12035-022-02837-z.

References

Brown J, Bianco J, McGrath J, Eyles D . 1,25-dihydroxyvitamin D3 induces nerve growth factor, promotes neurite outgrowth and inhibits mitosis in embryonic rat hippocampal neurons. Neurosci Lett. 2003; 343(2):139-43. DOI: 10.1016/s0304-3940(03)00303-3. View

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

Grundberg E, Brandstrom H, Ribom E, Ljunggren O, Mallmin H, Kindmark A . Genetic variation in the human vitamin D receptor is associated with muscle strength, fat mass and body weight in Swedish women. Eur J Endocrinol. 2004; 150(3):323-8. DOI: 10.1530/eje.0.1500323. View

Ding E, Mehta S, Fawzi W, Giovannucci E . Interaction of estrogen therapy with calcium and vitamin D supplementation on colorectal cancer risk: reanalysis of Women's Health Initiative randomized trial. Int J Cancer. 2007; 122(8):1690-4. DOI: 10.1002/ijc.23311. View

Kesby J, Burne T, McGrath J, Eyles D . Developmental vitamin D deficiency alters MK 801-induced hyperlocomotion in the adult rat: An animal model of schizophrenia. Biol Psychiatry. 2006; 60(6):591-6. DOI: 10.1016/j.biopsych.2006.02.033. View

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

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

Delis D, Freeland J, Kramer J, Kaplan E . Integrating clinical assessment with cognitive neuroscience: construct validation of the California Verbal Learning Test. J Consult Clin Psychol. 1988; 56(1):123-30. DOI: 10.1037//0022-006x.56.1.123. View

Roth S, Zmuda J, Cauley J, Shea P, Ferrell R . Vitamin D receptor genotype is associated with fat-free mass and sarcopenia in elderly men. J Gerontol A Biol Sci Med Sci. 2004; 59(1):10-5. DOI: 10.1093/gerona/59.1.b10. View

10.

Zonderman A, Giambra L, Arenberg D, Resnick S, Costa Jr P, Kawas C . Changes in immediate visual memory predict cognitive impairment. Arch Clin Neuropsychol. 1995; 10(2):111-23. View

11.

Vargas T, Bullido M, Martinez-Garcia A, Antequera D, Clarimon J, Rosich-Estrago M . A megalin polymorphism associated with promoter activity and Alzheimer's disease risk. Am J Med Genet B Neuropsychiatr Genet. 2010; 153B(4):895-902. DOI: 10.1002/ajmg.b.31056. View

12.

Gezen-Ak D, Dursun E, Ertan T, Hanagasi H, Gurvit H, Emre M . Association between vitamin D receptor gene polymorphism and Alzheimer's disease. Tohoku J Exp Med. 2007; 212(3):275-82. DOI: 10.1620/tjem.212.275. View

13.

Annweiler C, Schott A, Rolland Y, Blain H, Herrmann F, Beauchet O . Dietary intake of vitamin D and cognition in older women: a large population-based study. Neurology. 2010; 75(20):1810-6. DOI: 10.1212/WNL.0b013e3181fd6352. View

14.

Wang Y, Chiang Y, Su T, Hayashi T, Morales M, Hoffer B . Vitamin D(3) attenuates cortical infarction induced by middle cerebral arterial ligation in rats. Neuropharmacology. 2000; 39(5):873-80. DOI: 10.1016/s0028-3908(99)00255-5. View

15.

Folstein M, Folstein S, McHugh P . "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975; 12(3):189-98. DOI: 10.1016/0022-3956(75)90026-6. View

16.

Uitterlinden A, Fang Y, van Meurs J, van Leeuwen H, Pols H . Vitamin D receptor gene polymorphisms in relation to Vitamin D related disease states. J Steroid Biochem Mol Biol. 2004; 89-90(1-5):187-93. DOI: 10.1016/j.jsbmb.2004.03.083. View

17.

Kalueff A, Keisala T, Minasyan A, Kuuslahti M, Miettinen S, Tuohimaa P . Behavioural anomalies in mice evoked by "Tokyo" disruption of the Vitamin D receptor gene. Neurosci Res. 2006; 54(4):254-60. DOI: 10.1016/j.neures.2005.12.008. View

18.

Saporito M, Brown E, Hartpence K, Wilcox H, Vaught J, Carswell S . Chronic 1,25-dihydroxyvitamin D3-mediated induction of nerve growth factor mRNA and protein in L929 fibroblasts and in adult rat brain. Brain Res. 1994; 633(1-2):189-96. DOI: 10.1016/0006-8993(94)91539-3. View

19.

Ortlepp J, Lauscher J, Hoffmann R, Hanrath P, Joost H . The vitamin D receptor gene variant is associated with the prevalence of type 2 diabetes mellitus and coronary artery disease. Diabet Med. 2001; 18(10):842-5. DOI: 10.1046/j.1464-5491.2001.00585.x. View

20.

Petersen R . Mild cognitive impairment as a diagnostic entity. J Intern Med. 2004; 256(3):183-94. DOI: 10.1111/j.1365-2796.2004.01388.x. View