Beydoun May A, Tajuddin Salman M, Dore Greg A, Canas Jose-Atilio, Beydoun Hind A, Evans Michele K, Zonderman Alan B
National Institute on Aging, Intramural Research Program, NIH, Baltimore, MD;
National Institute on Aging, Intramural Research Program, NIH, Baltimore, MD.
J Nutr. 2017 Jun;147(6):1048-1062. doi: 10.3945/jn.116.244962. Epub 2017 Apr 26.
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.
维生素D受体（VDR）和[或低密度脂蛋白受体相关蛋白2（LRP2）]基因的纵向认知变化与多态性之间的联系仍不清楚，尤其是在非裔美国（AA）成年人中。我们旨在评估VDR基因的单核苷酸多态性（SNP）[rs11568820（Cdx-2：T/C）、rs1544410（BsmI：G/A）、rs7975232（ApaI：A/C）、rs731236（TaqI：G/A）]和LRP2基因的单核苷酸多态性[rs3755166：G/A、rs2075252：C/T、rs2228171：C/T]与认知各领域纵向认知表现变化的关联。我们使用了来自“跨生命周期多样性社区健康老龄化”研究（马里兰州巴尔的摩）的1024名有完整基因数据的AA城市成年参与者的数据，其中660 - 797人在基线和/或第一次随访检查时有9项认知测试分数的完整数据以及完整的协变量数据（约52%为女性；平均年龄：约52岁；平均受教育年限：12.6年）。第1次（2004 - 2009年）和第2次（2009 - 2013年）检查之间的时间间隔从<1年到约8年不等，平均±标准差为4.64±0.93年。通过创建与混合效应回归模型预测的认知变化纵向年率相关的基因多态性组进行潜在类别和单倍型分析。在主要发现中，rs3755166：G/A SNP与简易精神状态检查总体上更快的下降相关（β = -0.002，P = 0.018），在女性中也是如此。（BsmI/ApaI/TaqI：G-/A-/A-）SNP潜在类别[SNPLC；与（ApaI：“AA”）相比]与女性语言流畅性测试（分类）中更快的下降相关，其中（rs2228171：“TT”）SNPLC（与：rs2228171：“CC”相比）也与连线测验B部分（Trails B）中更快的下降相关，但与倒背数字广度（DS - B）中较慢的下降相关。此外，在男性中，VDR SNP单倍型（SNPHAP；GCA：baT）与Trails B中较慢的下降相关，而LRP2 SNPHAP（GCC）与DS - B中更快的下降相关，表现为认知领域2（“视觉/工作记忆”）中更快的下降。VDR和LRP2基因变异可在AA城市成年人的男性和女性中不同程度地改变与年龄相关的认知轨迹，特别是在整体精神状态以及语言流畅性、视觉/工作记忆和执行功能领域。
