National Institute on Aging, Intramural Research Program, NIH, Baltimore, MD, USA.
Am J Clin Nutr. 2012 Jan;95(1):163-78. doi: 10.3945/ajcn.111.017137. Epub 2011 Dec 14.
Vitamin D receptor (VDR) and the megalin gene polymorphism's link with longitudinal cognitive change remains unclear.
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.
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.
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.
Sex-specific VDR and Megalin gene variations can modify age-related cognitive decline among US adults.
维生素 D 受体 (VDR) 和 megalin 基因多态性与纵向认知变化的关系尚不清楚。
研究 VDR 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 megalin（rs3755166：G/A；rs2075252：C/T；rs4668123：C/T）基因与纵向认知表现变化的相关性。
本研究使用了巴尔的摩纵向衰老研究中 702 名非西班牙裔白人参与者的数据。通过线性混合模型，使用所有认知评分时间点（预测 I）或痴呆发病前的时间点（预测 II），预测认知变化的年率（LARCCs），分别为 50 岁时和个体平均随访年龄。进行了潜在类别、单倍型和最小二乘（OLS）回归分析。
在 OLS 模型中，以 SNP 潜在类别为 LARCCs 的预测因子，与 Megalin(1) [rs3755166(-)/rs2075252(CC)/rs4668123(-)]相比，Megalin(2) [rs3755166(-)/rs2075252(TT)/rs4668123(T-)]与男性的言语记忆下降相关（预测 II）。还发现 SNP 单倍型（SNPHAP）存在显著的性别差异。在女性中，VDR(1) [BsmI(G-)/ApaI(C-)/TaqI(A-); baT]与类别流畅性下降有关（预测 I：β=-0.031，P=0.012）。Megalin(1) SNPHAP（GCC）与女性的言语记忆、即刻回忆[加利福尼亚语言学习测试（CVLT），A 组；预测 II：β=-0.043，P=0.006]下降有关，但与男性的延迟回忆下降有关（CVLT-DR：β>0，P<0.0125；两种预测）。在女性中，Megalin(2) SNPHAP（ACC）与类别流畅性下降有关（预测 II：β=+0.026，P=0.005）。另一个发现是，Megalin SNP rs3755166：G/A 与两性的总体认知下降和男性的言语记忆下降有关。
美国成年人的维生素 D 受体和 megalin 基因的性别特异性变异可以改变与年龄相关的认知下降。
