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J Neurol Sci. 2017 Nov 15;382:13-17. doi: 10.1016/j.jns.2017.09.016. Epub 2017 Sep 12.

A complex association between ABCA7 genotypes and blood lipid levels in Southern Chinese Han patients of sporadic Alzheimer's disease.

Author information

1
Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
2
Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China. Electronic address: yangxsxy@126.com.
3
Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China. Electronic address: xiaobxy@126.com.

Abstract

Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by progressive cognitive decline. It can be divided into familial AD (FAD) and sporadic AD (SAD) based on the family history. Recently dysregulation of cholesterol homeostasis has been implicated in the development of late-onset AD. ATP-binding cassette transporter A7 (ABCA7) gene, regulating the transport of cholesterol, has been recently identified as a susceptible gene of AD by several large genome-wide association studies. To test the genetic effect of ABCA7 rs3764650 on blood lipid levels in Southern Chinese Han population and investigate the risk factors of SAD, a total of 118 SAD patients and 120 healthy matched controls were recruited and the genotyping in ABCA7 rs3764650 was conducted on the Sequenom MassARRAY iPLEX platform. Meanwhile, the levels of fasting lipid profile and mini-mental state examination (MMSE) scores were tested. There was significant difference in genotype distribution between SAD patients and controls (p=0.001). While the difference of ABCA7 rs3764650 allele distribution between SAD patients and controls was only significant in APOEε4-noncarriers (p=0.039). The association between blood lipid levels and ABCA7 rs3764650 genotypes was influenced by APOEε4 status. In APOEε4-noncarriers of SAD, the total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels in GG genotype group were significantly lower than those in GT and TT genotype groups (all p<0.05). Whereas no significant difference of blood lipid levels was found among three genotypes in APOEε4-carriers of SAD and controls. Additionally, logistic regression analysis showed that lower high-density lipoprotein cholesterol (HDL-C) levels (p=0.015, OR=5.669) and GG genotype (p=0.013, OR=8.318) were positively associated with SAD. Our results suggest that GG genotype of ABCA7 rs3764650 was a risk factor of SAD in Southern Chinese Han population as well as lipid homeostasis.

KEYWORDS:

ABCA7; Alzheimer's disease; Lipids; Single nucleotide polymorphism

PMID:
29111006
DOI:
10.1016/j.jns.2017.09.016
[Indexed for MEDLINE]

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