Genetic risk factors for longitudinal changes in structural MRI in former organolead workers.
Genetic risk factors for longitudinal changes in structural MRI in former organolead workers.
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DOI：
10.4061/2011/362189
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发表时间：
2011
影响因子：
4.7
通讯作者：
Schwartz BS
中科院分区：
文献类型：
--
作者：
James BD;Caffo B;Stewart WF;Yousem D;Davatzikos C;Schwartz BS
这项研究考察了载脂蛋白E(APOE)、血管紧张素转换酶(ACE)和维生素D受体(VDR)三个基因的多态性与脑体积和白质损伤(WML)的纵向变化以及心血管因素和胫骨铅浓度的影响之间的关系。对317名前有机铅工人和45名以人群为基础的对照组进行了两次平均相隔5年的磁共振成像。进行了感兴趣区和体素分析。载脂蛋白Eε3/ε4和ε4/ε4基因型与白质体积下降程度较小相关。有证据表明基因多态和心血管危险因素(血管紧张素转换酶和高密度脂蛋白；维生素D受体和糖尿病)在脑体积下降方面存在交互作用。VDR FokIff基因与WML的增加相关(与APOE或ACE无关)。这项研究扩大了我们对痴呆症和心血管疾病的遗传前驱与大脑结构变化之间的关系的理解。
This study examined associations between polymorphisms in three genes, apolipoprotein E (APOE), angiotensin converting enzyme (ACE), and vitamin D receptor (VDR), and longitudinal change in brain volumes and white matter lesions (WML) as well as effect modification by cardiovascular factors and tibia lead concentrations. Two MRIs, an average of 5 years apart, were obtained for 317 former organolead workers and 45 population-based controls. Both regions-of-interest and voxel-wise analyses were conducted. APOE ε3/ε4 and ε4/ε4 genotypes were associated with less decline in white matter volumes. There was some evidence of interaction between genetic polymorphisms and cardiovascular risk factors (ACE and high-density lipoprotein; VDR and diabetes) on brain volume decline. The VDR FokI ff genotype was associated with an increase in WML (no association for APOE or ACE). This study expands our understanding of how genetic precursors of dementia and cardiovascular diseases are related to changes in brain structure.