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Association of HMGCR polymorphism with late-onset Alzheimer's disease in Han Chinese

2016; Impact Journals LLC; Volume: 7; Issue: 16 Linguagem: Inglês

10.18632/oncotarget.8176

1949-2553

Xiaolong Chang, Lin Tan, Meng‐Shan Tan, Hui-Fu Wang, Chen‐Chen Tan, Wei Zhang, Zhan-Jie Zheng, Lingli Kong, Zixuan Wang, Teng Jiang, Jin‐Tai Yu, Lan Tan,

Alzheimer's disease research and treatments

// Xiao-Long Chang 1, * , Lin Tan 2, * , Meng-Shan Tan 3 , Hui-Fu Wang 4 , Chen-Chen Tan 3 , Wei Zhang 3 , Zhan-Jie Zheng 5 , Ling-Li Kong 5 , Zi-Xuan Wang 3 , Teng Jiang 6 , Jin-Tai Yu 3 , Lan Tan 1, 2, 3 1 Department of Neurology, Qingdao Municipal Hospital, Dalian Medical University, Qingdao, PR China 2 College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, PR China 3 Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, PR China 4 Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Qingdao, PR China 5 Department of Geriatric, Qingdao Mental Health Center, Qingdao, PR China 6 Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, PR China * These authors contributed equally to this work Correspondence to: Lan Tan, e-mail: dr.tanlan@163.com Jin-Tai Yu, e-mail: yu-jintai@163.com , Jintai.yu@ucsf.edu Keywords: Alzheimer's disease, HMGCR, rs3846662, polymorphism Received: January 26, 2016 Accepted: February 21, 2016 Published: March 18, 2016 ABSTRACT The 3-hydroxy-3-methylglutaryl-CoA reductase ( HMGCR ) acts as a potential genetic modifier for Alzheimer's disease (AD). Previous reports identified that HMGCR rs3846662 polymorphism is associated with biosynthesis of cholesterol in AD pathology. In order to assess the involvement of the HMGCR polymorphism in the risk of late-onset AD (LOAD) in northern Han Chinese, we performed a case–control study of 2334 unrelated subjects (984 cases and 1350 age- and gender-matched controls) to evaluate the genotype and allele distributions of the HMGCR rs3846662 with LOAD. The genotype distribution (GG, AG, AA) of rs3846662 was significantly different between LOAD patients and controls ( P = 0.003), but the allele distribution did not reach a significant difference ( P = 0.614). After adjusting for age, gender and the APOE ε4 status, the minor A allele of rs3846662 was validated as a protective factor for LOAD in dominant model (OR = 0.796, P = 0.02, 95% CI = 0.657–0.965). Interestingly, we observed rs3846662 polymorphism was only significantly associated with LOAD in APOE ε4 non-carriers (OR = 0.735, P = 0.005, 95% CI = [0.593, 0.912]). In conclusion, our study demonstrates A allele of HMGCR rs3846662 acts as a protective factor for LOAD in northern Han Chinese.