Dataset Information

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

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 (? = -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.

SUBMITTER: Beydoun MA

PROVIDER: S-EPMC5443463 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Beydoun May A MA Tajuddin Salman M SM Dore Greg A GA Canas Jose-Atilio JA Beydoun Hind A HA Evans Michele K MK Zonderman Alan B AB

The Journal of nutrition 20170426 6

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,rs2075 ...[more]

PMID: 28446629

Similar Datasets

Project description:BackgroundVitamin D receptor (VDR) and the megalin gene polymorphism's link with longitudinal cognitive change remains unclear.ObjectiveThe 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.DesignData 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.ResultsAmong 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.ConclusionSex-specific VDR and Megalin gene variations can modify age-related cognitive decline among US adults.

Project description:We examined longitudinal associations of vitamin D receptor (VDR) and megalin (LRP2; LDL receptor-related protein-2) gene polymorphisms with central adiposity. We used data from the Baltimore Longitudinal Study of Aging (BLSA), an ongoing prospective open cohort study. Study participants consisted of non-Hispanic white adults residing in Baltimore city, with one or more visits at age ≥50 years, and complete data (n 609-617). Repeated assessments on waist circumference (WC) and waist:hip ratio (WHR) were available. Multiple linear mixed models were used to estimate mid-follow-up age central adiposity level and annual rate of change with cut-points set at the sex-specific 80th percentile. The four binary outcomes were: 'elevated central adiposity' (ECA-WC and ECA-WHR) and 'significant increase in central adiposity' (SICA-WC and SICA-WHR). SNP for VDR (four SNP: (1) rs11568820 (CdX-2:T/C); (2) rs1544410 (BsmI:G/A); (3) rs7975232 (ApaI:A/C); (4) rs731236 (TaqI:G/A)) and Megalin (three SNP: (1) rs3755166:G/A; (2) rs2075252:C/T; (3) rs4668123:C/T) genes were selected. SNP latent classes (SNPLC) and SNP haplotypes (SNPHAP) were created. Multiple logistic regression analyses indicated that, in men, higher ECA-WHR odds were associated with SNPLC Megalin2:rs3755166[-]/rs2075252[TT]/rs4668123[T-] (v. Megalin1:rs3755166[-]/rs2075252[CC]/rs4668123[-]) (OR 2·87; 95 % CI 1·15, 7·12; P = 0·023) and that SNPLC Megalin3:rs3755166[-]/rs2075252[CT]/rs4668123[-] (v. Megalin1) was linked to lower SICA-WC odds (OR 0·48; 95 % CI 0·26, 0·88; P = 0·019) (P > 0·05 for sex × SNPLC). In women, VDR3 SNPHAP (GAA:bAT) was related to lower odds of ECA-WC (OR 0·37; 95 % CI 0·16, 0·87; P = 0·023) (P < 0·05 for sex × SNPHAP), VDR1 SNPHAP (GCA:baT) was associated with greater odds and VDR3 SNPHAP (GAA:bAT) with lower odds of SICA-WC (P > 0·05 for sex × SNPHAP). Vitamin D-related gene polymorphisms were associated with central adiposity status and change. Future mechanistic studies are needed to confirm those polymorphisms' biological significance to central adiposity.

Project description:Recent evidence indicates that thyroid hormones may be closely linked to cognition among adults. We investigated associations between thyroid hormones and longitudinal cognitive change, within and outside of reference ranges, stratifying by sex and race. This longitudinal study used data from the Healthy Aging in Neighborhoods of Diversity Across the Lifespan study, set in Baltimore City, MD, 2004-2013, on adults aged 30-64 years at baseline visit, with a length of follow-up between visits 1 and 2 ranging from <1 to 8 years; mean ± standard deviation: 4.64 ± 0.93. The final analytic sample sizes ranged from 1486 to 1602 participants with 1.6-1.7 visits per participant (total visits: 2496-2757), depending on the cognitive test. Eleven cognitive test scores spanning domains of learning or memory, language or verbal, attention, visuospatial and/or visuoconstruction, psychomotor speed, executive function, and mental status were used. Mixed-effects regression models were conducted, interacting time of follow-up with several thyroid exposures. Whites performed better than African Americans, with only 4 cognitive test scores of 11 declining significantly over time. Importantly, above reference range thyroid stimulating hormone (vs. reference range, thyroid stimulating hormone, above reference range [TSHarr]) was linked to faster rates of decline on the digits span backwards test, reflecting working memory (TSHarr × time γ ± standard error: -0.14 ± 0.05, p = 0.006) and clock-command, at test of visuospatial and/or visuoconstruction abilities (TSHarr × Time γ ± standard error: -0.10 ± 0.04, p = 0.004). The latter finding was replicated when comparing normal thyroid function to "subclinical hypothyroidism". Within-reference ranges, a higher thyroid stimulating hormone was related to faster decline on the clock-command test scores in women. In sum, higher baseline thyroid stimulating hormone was associated with faster cognitive decline over-time among urban US adults, specifically in domains of working memory and visuospatial and/or visuoconstruction abilities.

Project description:BACKGROUND:Chronic systemic inflammation has been positively associated with structural and functional brain changes representing early markers of Alzheimer's Disease (AD) and cognitive decline. The current study examined associations between systemic inflammation and cognitive performance among African-Americans and Whites urban adults. METHODS:Participants were selected from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study (2004-2013, baseline age: 30-64?y, mean?±?SD follow-up time of 4.64?±?0.93?y, N?=?189-222, k?=?1.5-1.7 observations/participant). Cytokines known to be positively linked to AD incidence among others were tested against cross-sectional and longitudinal cognitive function, stratifying by age group (?50?y vs. >50?y), sex and race. A series of mixed-effects regression models were conducted, adjusting for key confounders. RESULTS:Among key findings, IL1? was positively associated with a faster rate of decline on a test of executive functioning, among older adults (age >50?y, ?11?=?+2.49?±?0.89, p?=?0.005), while in the total population, IL-6 was linked to a faster decline on a test of verbal memory (?11?=?-0.011?±?0.004, p?=?0.009). Among younger participants, IL-18 was linked to a poorer performance on a test of attention at baseline (age ?50?y, ?01?=?-0.007?±?0.0025, p?=?0.004) though a slower rate of decline with higher IL-18 was detected for a test of psychomotor speed in older adults (age >50?y, ?11?=?+0.0010?±?0.0004, p?=?0.008). Finally, among Whites, unlike among African-Americans, IL-6 was associated with a better baseline performance on two tests of verbal and working memory. CONCLUSIONS:Cytokines were shown to be associated with age-related cognitive decline among middle-aged and older urban adults in an age group and race-specific manner. Further longitudinal studies are needed to replicate our findings and mediation through relevant biological and psychosocial factors need to be studied as well.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets