The ARNTL polymorphism rs900147 is associated with the risk of Alzheimer’s disease and amnestic mild cognitive impairment in a Chinese population

ABSTRACT

Recently, we discovered that single nucleotide polymorphisms (SNPs) ARNTL rs900147 and PER1 rs2253820 were significantly associated with Parkinson’s disease (PD). Both ARNTL and PER1 play essential roles in regulating the circadian rhythm, and disruption of the circadian system leads to an increased likelihood of developing both Alzheimer’s disease (AD) and PD. Therefore, it is reasonable to speculate that these SNPs may also be of relevance to AD as well as to amnestic mild cognitive impairment (aMCI), the prodromal (predementia) phase of AD. To test this hypothesis, we genotyped rs900147 and rs2253820 in 136 AD patients, 151 aMCI patients, and 257 healthy controls from a Chinese population using direct sequencing. A significant difference was observed for rs900147 between AD and control subjects regarding the genotypic distribution (p = 0.001) and allele frequency (p = 0.001), as well as between aMCI and control subjects regarding the genotypic distribution (p = 0.046) and allele frequency (p = 0.020). Carriers of the G allele were shown to be significantly more prone to developing AD and aMCI than other carriers. No significant difference was observed for rs2253820. This study revealed that variations in ARNTL are associated with AD/aMCI, and may represent genetic risk factors for AD/aMCI.

KEYWORDS:

• Alzheimer’s disease (AD)
• amnestic mild cognitive impairment (aMCI)
• ARNTL
• association study
• single nucleotide polymorphism (SNP)

Acknowledgments

We thank the patients and their families for their participation in this study. We thank Sarah Williams, PhD, from Liwen Bianji, Edanz Group China (www.liwenbianji.cn), for editing the English text of a draft of this manuscript.

Data availability statement

Raw data were generated at [Sangon, Shanghai, China]. Derived data supporting the findings of this study are available from the corresponding author [Yanning Cai] on request.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the National Key R&D Program of China (grant numbers 2017YFC0909103 and 2017YFC0909100), the National Natural Science Foundation of China (81671246), and the Beijing Municipal Commission of Health and Family Planning (grant numbers PXM2017-026283-000002 and PXM2018-026283-000002).