The polymorphism of CLOCK gene rs4864548 A>G is associated with susceptibility of Alzheimer’s disease in Chinese population

Abstract

The aim of this study was to investigate the correlation between polymorphism of circadian locomotor output cycle kaput (CLOCK) gene rs4864548 A/G and susceptibility of Alzheimer’s disease (AD). A total of 296 unrelated AD patients and 423 control subjects were enrolled in the case-control study. Genotypes of apolipoprotein E (APOE) and CLOCK gene rs4864548 A/G were determined by a Polymerase Chain Reaction (PCR) restriction fragment length polymorphism detection method. Our results showed that in the whole sample or APOE ε 4 non-carriers, prevalence of A carriers in CLOCK gene rs4864548 A/G in AD patients was remarkably higher than that in control subjects (in the whole sample: χ² = 47.614, p < 0.0001; in APOE ε 4 non-carriers: χ² = 22.493, p < 0.0001). However, among APOE ε 4 carriers, the difference in the prevalence of A carriers in CLOCK gene rs4864548 A/G between AD patients and controls was no statistically significant (χ² = 0.669, p = 0.379). These findings demonstrate that A carriers in CLOCK gene rs 4864548 A/G were closely related to a high susceptibility of AD among APOE ε 4 non-carriers while the functional polymorphism of CLOCK gene rs4864548 A/G was not associated with the susceptibility of AD among APOE ε 4 carriers.

Keywords:

• CLOCK gene rs4864548A/G
• polymorphism
• Alzheimer’s disease
• susceptibility
• genetic risk factor

Acknowledgments

The authors thank the staff of the Key Laboratory of Chronobiology of Health Ministry in Basic and Forensic School of Sichuan University, and the Department of Geriatrics of the third hospital of Mianyang, and all study participants (as well as their legal proxies) for their great contributions.