Jianxiong Xi, Ding Ding*, Qianhua Zhao, Xiaoniu Liang, Li Zheng, Qihao Guo, Zhen Hong, Hua Fu, Jianfeng Xu and Qianyi Xiao* Pages 185 - 195 ( 11 )
Background: Approximately 40 independent Single Nucleotide Polymorphisms (SNPs) have been associated with Alzheimer’s Disease (AD) or cognitive decline in genome-wide association studies.
Objective: 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. Methods: 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. Results: 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). Conclusion: 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.Mild cognitive impairment, progression, Alzheimer’s disease, ABCA7, body mass index, risk factor.
Department of Preventive Medicine and Health Education, School of Public Health, Fudan University, Shanghai, Institute of Neurology, Huashan Hospital, Fudan University, Shanghai, Institute of Neurology, Huashan Hospital, Fudan University, Shanghai, Institute of Neurology, Huashan Hospital, Fudan University, Shanghai, Institute of Neurology, Huashan Hospital, Fudan University, Shanghai, Institute of Neurology, Huashan Hospital, Fudan University, Shanghai, Institute of Neurology, Huashan Hospital, Fudan University, Shanghai, Department of Preventive Medicine and Health Education, School of Public Health, Fudan University, Shanghai, Department of Preventive Medicine and Health Education, School of Public Health, Fudan University, Shanghai, Department of Preventive Medicine and Health Education, School of Public Health, Fudan University, Shanghai