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.
Highlights
Alzheimer’s disease (AD), as the most common type of dementia for the aged people, is a multifactorial disease with complex etiology over genetic and environmental factors [1, 2]
The presence of the apolipoprotein E (APOE) ε4 significantly raised the risk of late-onset AD (LOAD) in cases compared with control subjects (P = 0.0001, odds ratio (OR) = 2.413, 95% confidence interval (CI) = 1.963 – 2.967)
We found that the rs3846662 significantly protected LOAD in dominant model (OR = 0.796, P = 0.02, 95% CI = [0.657, 0.965])
Summary
Alzheimer’s disease (AD), as the most common type of dementia for the aged people, is a multifactorial disease with complex etiology over genetic and environmental factors [1, 2]. The late-onset AD (LOAD) is identified as the most common form and has a complex genetic issue. Only the ε4 allele of apolipoprotein E (APOE) gene has been identified unequivocally as a major genetic factor to LOAD. Recent several large genome-wide association studies (GWAS) based on Caucasians have identified numbers of several risk genes that may affect LOAD susceptibility [4, 5]. These GWAS-linked loci still could not fully account for the genetic factor of LOAD, indicating that there are additional risk loci for LOAD remaining to be discovered [6]
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