Department of Preventive Medicine and Health Education, School of Public Health, Fudan University, Shanghai, China.
Institute of Neurology, Huashan Hospital, Fudan University, Shanghai, China.
Curr Alzheimer Res. 2020;17(2):185-195. doi: 10.2174/1567205017666200317095608.
Approximately 40 independent Single Nucleotide Polymorphisms (SNPs) have been associated with Alzheimer's Disease (AD) or cognitive decline in genome-wide association studies.
We aimed to evaluate the joint effect of genetic polymorphisms and environmental factors on the progression from Mild Cognitive Impairment (MCI) to AD (MCI-AD progression) in a Chinese community cohort.
Demographic, DNA and incident AD diagnosis data were derived from the follow-up of 316 participants with MCI at baseline of the Shanghai Aging Study. The associations of 40 SNPs and environmental predictors with MCI-AD progression were assessed using the Kaplan-Meier method with the log-rank test and Cox regression model.
Rs4147929 at ATP-binding cassette family A member 7 (ABCA7) (AG/AA vs. GG, hazard ratio [HR] = 2.43, 95% confidence interval [CI] 1.24-4.76) and body mass index (BMI) (overweight vs. non-overweight, HR = 0.41, 95% CI 0.22-0.78) were independent predictors of MCI-AD progression. In the combined analyses, MCI participants with the copresence of non-overweight BMI and the ABCA7 rs4147929 (AG/AA) risk genotype had an approximately 6-fold higher risk of MCI-AD progression than those with an overweight BMI and a non-risk genotype (HR = 6.77, 95% CI 2.60-17.63). However, a nonsignificant result was found when participants carried only one of these two risk factors (nonoverweight BMI and AG/AA of ABCA7 rs4147929).
ABCA7 rs4147929 and BMI jointly affect MCI-AD progression. MCI participants with the rs4147929 risk genotype may benefit from maintaining an overweight BMI level with regard to their risk for incident AD.
在全基因组关联研究中，大约有 40 个独立的单核苷酸多态性（SNP）与阿尔茨海默病（AD）或认知能力下降相关。
我们旨在评估遗传多态性和环境因素对中国社区队列中从轻度认知障碍（MCI）到 AD（MCI-AD 进展）的进展的联合影响。
人口统计学、DNA 和 AD 发病诊断数据来自上海老龄化研究基线时 316 名 MCI 参与者的随访。使用 Kaplan-Meier 方法和对数秩检验以及 Cox 回归模型评估 40 个 SNP 和环境预测因子与 MCI-AD 进展的相关性。
ATP 结合盒家族 A 成员 7（ABCA7）的 rs4147929（AG/AA 与 GG，风险比 [HR] = 2.43，95%置信区间 [CI] 1.24-4.76）和体重指数（BMI）（超重与非超重，HR = 0.41，95%CI 0.22-0.78）是 MCI-AD 进展的独立预测因子。在联合分析中，MCI 参与者同时存在非超重 BMI 和 ABCA7 rs4147929（AG/AA）风险基因型，与 BMI 超重和非风险基因型相比，MCI-AD 进展的风险大约增加 6 倍（HR = 6.77，95%CI 2.60-17.63）。然而，当参与者仅携带这两个危险因素中的一个时，结果并不显著（非超重 BMI 和 ABCA7 rs4147929 的 AG/AA）。
ABCA7 rs4147929 和 BMI 共同影响 MCI-AD 进展。携带 rs4147929 风险基因型的 MCI 参与者可能受益于保持超重 BMI 水平，以降低其患 AD 的风险。
