Vitamin D receptor and megalin gene polymorphisms and their associations with longitudinal cognitive change in US adults
Vitamin D receptor and megalin gene polymorphisms and their associations with longitudinal cognitive change in US adults
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DOI：
10.3945/ajcn.111.017137
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发表时间：
2012-01-01
影响因子：
7.1
通讯作者：
Zonderman, Alan B.
中科院分区：
文献类型：
--
作者：
Beydoun, May A.;Ding, Eric L.;Zonderman, Alan B.
目的：研究维生素D受体(VDR)基因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)基因与纵向认知能力改变的关系。用线性混合模型预测50岁至个体平均随访年龄之间的认知改变年率(LARCCs)，使用所有认知得分时间点(预测I)或痴呆发病前的时间点(预测II)。结果：在以SNP潜伏期作为LARCC预测因子的OLS模型中，与megalin(1)[rs3755166(-)/rs2075252(TT)/rs4668123(T-)]相比，megalin(2)[rs3755166(-)/rs2075252(CC)/rs4668123(-)]与megalin(1)[rs3755166(-)/rs2075252(CC)/rs4668123(-)]相比，男性言语记忆能力下降更大(预测II)。SNP单倍型(SNPHAP)也存在显著的性别差异。在女性中，VDR1[BsmI(G-)/Apai(C-)/Taqi(A-)；BAT]与类别流畅性的更大下降有关(预测I：β=-0.031，P=0.012)。Megalin1SNPHAP(GCC)与女性在言语记忆、即时回忆方面的下降幅度较大[加州言语学习测试，列表A；预测II：Beta=-0.043，P=0.006]有关，但与男性延迟回忆能力下降较慢有关(CVLT-DR：Beta>；0，P<；0.0125；两项预测都是如此)。在女性中，Megalin2SNPHAP(Acc)与类别流畅性下降较慢相关(预测II：Beta=+0.026，P=0.005)。另一项发现是，megalin SNP rs3755166：G/A与男女总体认知和男性言语记忆的严重下降有关。结论：性别特有的VDR和megalin基因变异可以改变美国成年人的年龄相关性认知下降。AM J Clin Nutr 2012；95：163-78。
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, VDR1 [BsmI (G-)/ApaI(C-)/TaqI(A-); baT] was linked to a greater decline in category fluency (prediction I: beta = -0.031, P = 0.012). The Megalin1 SNPHAP (GCC) was related to greater decline among women for verbal memory, immediate recall [California Verbal Learning Test (CVLT), List A; prediction II: beta = -0.043, P = 0.006) but to slower decline among men for delayed recall (CVLT-DR: beta > 0, P < 0.0125; both predictions). In women, the Megalin2 SNPHAP (ACC) was associated with slower decline in category fluency (prediction II: beta = +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. Am J Clin Nutr 2012;95:163-78.