Complement receptor 1 genetic polymorphism contributes to sporadic Alzheimer's disease susceptibility in Caucasians: a meta-analysis.

Hai Yuan,Pingping Ge,Lingling Du

doi:10.1042/bsr20200321

Abstract

Complement receptor 1 (CR1) plays an important role in the development of sporadic Alzheimer’s disease (SAD) in Caucasians. However, the influence of CR1 (rs6656401A/G and rs3818361T/C) genetic polymorphisms on the risk of SAD remains controversial. A meta-analysis of 18 case–control studies was performed to derive a more precise association of CR1 (rs6656401A/G or rs3818361T/C) genetic polymorphism with the risk of SAD in Caucasians. A statistical difference was found in the dominant model (odds ratio (OR): 1.23, 95% confidence interval (CI): 1.16–1.30, P=0.00), recessive model (OR: 1.28, 95% CI: 1.05–1.56, P=0.02), homozygote comparison (OR: 1.36, 95% CI: 1.12–1.66, P=0.002) or heterozygote comparison (AG versus GG) (OR: 1.21, 95% CI: 1.15–1.29, P=0.00) of CR1 rs6656401A/G. For CR1 rs3818361T/C, a statistical difference was observed in the dominant model (OR: 1.21, 95% CI: 1.13–1.31, P=0.00), recessive model (OR: 1.28, 95% CI: 1.07–1.53, P=0.006), homozygote comparison (OR: 1.35, 95% CI: 1.13–1.62, P=0.001) or heterozygote comparison (TC versus CC) (OR: 1.20, 95% CI: 1.11–1.29, P=0.00). In summary, despite some limitations, the present meta-analysis indicated that rs6656401A/G or rs3818361T/C polymorphism was related to SAD risk. Moreover, a carrier of rs6656401A/G or T carrier of rs3818361T/C in CR1 genetic polymorphism might be an increased factor for SAD in Caucasians.

Highlights

Alzheimer’s disease (AD) is the most common neurodegenerative disease causing progressive memory impairment and cognitive dysfunction among elderly people [1,2]
Another study found that the SNP rs6656401A/G was associated with AD risk, and rs3818361 T/C was related to AD risk in APOEε4 carriers [50]
An association of rs3818361T/C with a low amyloid burden was observed in the brain of AD patients, which emphasized the potential implication of Complement receptor 1 (CR1) in the brain amyloid pathway [52]

Summary

Introduction

Alzheimer’s disease (AD) is the most common neurodegenerative disease causing progressive memory impairment and cognitive dysfunction among elderly people [1,2]. The pathological hallmark of the disease is the accumulation of amyloid plaques in the brain, which leads to neurodegeneration [3]. Increasing evidence points to an important role of immunopathological processes in AD pathogenesis. Activated microglia and astrocytes produce strong immunopathological responses, which have been considered to contribute to AD neurodegeneration [4,5]. Several research and clinical trials have shown that immunopathological responses are a key feature in AD brain [6], there is no effective treatment for this terminal disease. CR1 was postulated to be a key factor for AD pathogenesis due to its role in regulating complement activity by acting as a receptor of complement C3b protein [12].

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