Association of ABCA1 rare nonsynonymous variants with primary open angle glaucoma

Authors: Xu Yuxia,  Huang Lulin,  Gong Bo,  Chen Yuhong,  Sun Xinghuai,  Yang Zhenglin

DOI: 10.3760/cma.j.issn.2095-0160.2019.06.007
Published 2019-06-10
Cite as Chin J Exp Ophthalmol, 2019,37(6): 439-445.

Abstract

Objective

To explore the rare nonsynonymous variants of ABCA1 gene in primary open angle glaucoma (POAG).

Methods

A prospective cohort study was carried out.Three hundred and ninety-eight POAG patients and 198 healthy controls matched in age and gender were recruited from March 2017 to March 2018 in Eye and Ear Nose Throat (ENT) Hospital of Fudan University.The periphery blood of 2-5 ml from all the subjects was collected for extraction of DNA, and rare variant analysis of the ABCA1 gene was conducted by whole exome sequencing (WES) data of these subjects.The study protocol was approved by Ethic Committee of Eye and Ear Nose Throat Hospital of Fudan University and Sichuan Provincial People’s Hospital (No.2016-32-1), and written informed consent was obtained from each subject prior to entering the study cohort.

Results

A total of 21 rare nonsynonymous variants (minor allele frequency MAF<0.01) were detected in the coding regions of ABCA1 gene in 27 subjects of the 398 POAG, with the detection rate of 6.8%.Among them, c.4310C>A (p.Thr1437Asn), c.3772G>T(p.Asp1258Tyr), c.775A>G (p.Lys259Glu) and c. 1507_1508insGAGGT (p.Glu503GlyfsX7) were four novel variants.In the 198 healthy controls, five rare nonsynonymous variants were detected in the ABCA1 gene from five subjects respectively, with the detection rate of 2.5%, the detection rate of nonsynonymous in POAG group was higher than that in healthy control group, showing a significant difference (χ2=4.72, P=0.03, OR=2.81).

Conclusions

Rare nonsynonymous variants in ABCA1 is associated with the pathogenesis of POAG.These variants can enrich the variation spectrum of ABCA1.

Key words:

Glaucoma, Open angle/genetics; Genetic variation; Sequence analysis, DNA/methods; Nonsynonymous variants; Whole exome sequencing; ABCA1 gene

Contributor Information

Xu Yuxia
Medical Technology College, Chengdu University of Traditional Chinese Medicine of China, Chengdu 610075, China
Huang Lulin
The Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China
Gong Bo
The Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China
Chen Yuhong
Department of Ophthalmology and Visual Science, Eye and Ear Nose Throat (ENT) Hospital, Shanghai Medical School, Fudan University, Shanghai 200031, China
Sun Xinghuai
Department of Ophthalmology and Visual Science, Eye and Ear Nose Throat (ENT) Hospital, Shanghai Medical School, Fudan University, Shanghai 200031, China
Yang Zhenglin
The Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, China
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