May A Beydoun1, Salman M Tajuddin2, Greg A Dore2, Jose-Atilio Canas3, Hind A Beydoun4, Michele K Evans2, Alan B Zonderman2. 1. National Institute on Aging, Intramural Research Program, NIH, Baltimore, MD; baydounm@mail.nih.gov. 2. National Institute on Aging, Intramural Research Program, NIH, Baltimore, MD. 3. Pediatric Endocrinology, Diabetes, and Metabolism, Nemour's Children's Clinic, Jacksonville, FL; and. 4. Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD.
Abstract
Background: The link between longitudinal cognitive change and polymorphisms in the vitamin D receptor (VDR) and MEGALIN [or LDL receptor-related protein 2 (LRP2)] genes remains unclear, particularly among African-American (AA) adults. Objectives: We aimed to evaluate 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 LRP2 [rs3755166:G/A,rs2075252:C/T, rs2228171:C/T] genes with longitudinal cognitive performance change in various domains of cognition. Methods: 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. Results: Among key findings, the rs3755166:G/A MEGALIN SNP was associated with faster decline on the Mini-Mental State Examination overall (β = -0.002, P = 0.018) and among women. VDR2 (BsmI/ApaI/TaqI: G-/A-/A-) SNP latent class [SNPLC; compared with VDR1 (ApaI: "AA")] was linked to faster decline on the Verbal Fluency Test, Categorical, in women, among whom the MEGALIN2 (rs2228171: "TT") SNPLC (compared with MEGALIN1: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 VDR1 SNP haplotype (SNPHAP; GCA:baT) was associated with a slower decline on the Trails B, whereas the MEGALIN1 SNPHAP (GCC) was associated with a faster decline on the DS-B, reflected as a faster decline on cognitive domain 2 ("visual/working memory"). Conclusion: VDR and MEGALIN 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.
Background: The link between longitudinal cognitive change and polymorphisms in the vitamin D receptor (VDR) and MEGALIN [or LDL receptor-related protein 2 (LRP2)] genes remains unclear, particularly among African-American (AA) adults. Objectives: We aimed to evaluate 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 LRP2 [rs3755166:G/A,rs2075252:C/T, rs2228171:C/T] genes with longitudinal cognitive performance change in various domains of cognition. Methods: 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. Results: Among key findings, the rs3755166:G/A MEGALIN SNP was associated with faster decline on the Mini-Mental State Examination overall (β = -0.002, P = 0.018) and among women. VDR2 (BsmI/ApaI/TaqI: G-/A-/A-) SNP latent class [SNPLC; compared with VDR1 (ApaI: "AA")] was linked to faster decline on the Verbal Fluency Test, Categorical, in women, among whom the MEGALIN2 (rs2228171: "TT") SNPLC (compared with MEGALIN1: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 VDR1 SNP haplotype (SNPHAP; GCA:baT) was associated with a slower decline on the Trails B, whereas the MEGALIN1 SNPHAP (GCC) was associated with a faster decline on the DS-B, reflected as a faster decline on cognitive domain 2 ("visual/working memory"). Conclusion:VDR and MEGALIN 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.
Authors: May A Beydoun; Adel Boueiz; Marwan S Abougergi; Melissa H Kitner-Triolo; Hind A Beydoun; Susan M Resnick; Richard O'Brien; Alan B Zonderman Journal: Neurobiol Aging Date: 2010-07-08 Impact factor: 4.673
Authors: B V Zlokovic; C L Martel; E Matsubara; J G McComb; G Zheng; R T McCluskey; B Frangione; J Ghiso Journal: Proc Natl Acad Sci U S A Date: 1996-04-30 Impact factor: 11.205
Authors: Matthew R Durk; Kyung Han; Edwin C Y Chow; Rosemary Ahrens; Jeffrey T Henderson; Paul E Fraser; K Sandy Pang Journal: J Neurosci Date: 2014-05-21 Impact factor: 6.167
Authors: Annette Hammes; Thomas K Andreassen; Robert Spoelgen; Jens Raila; Norbert Hubner; Herbert Schulz; Jochen Metzger; Florian J Schweigert; Peter B Luppa; Anders Nykjaer; Thomas E Willnow Journal: Cell Date: 2005-09-09 Impact factor: 41.582
Authors: A Nykjaer; D Dragun; D Walther; H Vorum; C Jacobsen; J Herz; F Melsen; E I Christensen; T E Willnow Journal: Cell Date: 1999-02-19 Impact factor: 41.582
Authors: Marcelo O Dietrich; Carlos Spuch; Dessire Antequera; Izaskun Rodal; Justo G de Yébenes; José Antonio Molina; Felix Bermejo; Eva Carro Journal: Neurobiol Aging Date: 2007-02-26 Impact factor: 4.673
Authors: Maris Kuningas; Simon P Mooijaart; Jelle Jolles; P Eline Slagboom; Rudi G J Westendorp; Diana van Heemst Journal: Neurobiol Aging Date: 2007-08-21 Impact factor: 4.673
Authors: May A Beydoun; Sharmin Hossain; Marie T Fanelli-Kuczmarski; Hind A Beydoun; Jose-Atilio Canas; Michele K Evans; Alan B Zonderman Journal: J Clin Endocrinol Metab Date: 2018-04-01 Impact factor: 5.958
Authors: May A Beydoun; Sharmin Hossain; Salman M Tajuddin; Jose A Canas; Marie Kuczmarski; Hind A Beydoun; Michele K Evans; Alan B Zonderman Journal: Sci Rep Date: 2018-05-23 Impact factor: 4.379
Authors: Katsuyuki Matsushita; Kiyoshi Mori; Turgay Saritas; Mahaba B Eiwaz; Yoshio Funahashi; Megan N Nickerson; Jessica F Hebert; Adam C Munhall; James A McCormick; Motoko Yanagita; Michael P Hutchens Journal: J Am Soc Nephrol Date: 2021-08-02 Impact factor: 14.978