摘要目的 对原发性开角型青光眼(POAG)患者ABCA1基因编码区变异进行分析,探讨ABCA1基因稀有非同义变异在POAG患者中的分布情况. 方法 采用前瞻性队列研究方法,自2017年3月至2018年3月共招募复旦大学附属眼耳鼻喉科医院就诊的POAG患者398例,并招募同期就诊的年龄和性别匹配的健康对照者198人.采集受检者外周静脉血2～5 ml,提取基因组DNA,利用全外显子测序(WES)技术对受检者ABCA1基因50个外显子区的稀有非同义变异进行测序和分析. 结果 POAG患者ABCA1基因稀有非同义变异检出率为6.8％ (27/398),发现21个稀有非同义变异位点,其中有4个新变异,包括c.4310C＞A(p.Thr1437Asn)、c.3772G＞T(p.Asp1258Tyr)、c.775A＞G (p.Lys259Glu)和c.1507_1508insGAGGT(p.Glu503GlyfsX7).健康对照者ABCA1稀有变异检出率为2.5％ (5/198),PGAG患者ABCA1稀有变异检出率明显高于健康对照者,差异有统计学意义(x2=4.72,P=0.03,OR=2.81).结论 ABCA1的稀有非同义变异与POAG发病有一定关联,丰富了ABCA1基因的稀有变异谱.

abstractsObjective 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.O1) 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 (x2=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.