Association of HMGCR polymorphism with late-onset Alzheimer′s disease in Han Chinese
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Xiao-Long Chang1,*, Lin Tan2,*, Meng-Shan Tan3, Hui-Fu Wang4, Chen-Chen Tan3, Wei Zhang3, Zhan-Jie Zheng5, Ling-Li Kong5, Zi-Xuan Wang3, Teng Jiang6, Jin-Tai Yu3, Lan Tan1,2,3
1Department of Neurology, Qingdao Municipal Hospital, Dalian Medical University, Qingdao, PR China
2College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, PR China
3Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, PR China
4Department of Neurology, Qingdao Municipal Hospital, Nanjing Medical University, Qingdao, PR China
5Department of Geriatric, Qingdao Mental Health Center, Qingdao, PR China
6Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, PR China
*These authors contributed equally to this work
Lan Tan, e-mail: [email protected]
Keywords: Alzheimer’s disease, HMGCR, rs3846662, polymorphism
Received: January 26, 2016 Accepted: February 21, 2016 Published: March 18, 2016
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.
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