Gong Bo, Qu Chao, Li Xiulan, Shi Yi, Lin Ying, Zhou Yu, Shuai Ping, Yang Yin, Liu Xiaoqi, Zhang Dingding, Yang Zhenglin
Sichuan Key Laboratory for Disease Gene Study, Hospital of University of Electronic Science and Technology of China & Sichuan Provincial People's Hospital, Chengdu, Sichuan, China School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China Sichuan Translational Medicine Research Hospital, Chinese Academy of Sciences, Chengdu, Sichuan, China.
School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China Sichuan Translational Medicine Research Hospital, Chinese Academy of Sciences, Chengdu, Sichuan, China Department of Ophthalmology, Hospital of University of Electronic Science and Technology of China & Sichuan Provincial People's Hospital, Chengdu, Sichuan, China.
Br J Ophthalmol. 2015 Mar;99(3):425-30. doi: 10.1136/bjophthalmol-2014-306054. Epub 2014 Dec 19.
The CYP1B1 gene has been shown to be related to primary open-angle glaucoma (POAG). This study aimed to identify the mutation profile of CYP1B1 in Chinese individuals with POAG.
The study included 416 unrelated cases diagnosed as POAG by standard ophthalmological examinations, and 657 unrelated healthy controls in a Chinese population. Genomic DNA was collected from peripheral blood of all the participants. The coding sequence of CYP1B1 was amplified by PCR from genomic DNA, followed by direct DNA sequencing.
Among 416 patients with POAG, 13 missense mutations, including nine reported mutations and four novel mutations (p.P93S, p.R259C, p.A295T, p.L475P), were detected in 25 patients. All these mutations were found as heterozygotes and the reported mutations have been previously found in primary congenital glaucoma and/or POAG patients. Three of them (p.L107V, p.E229K, p.V320L) were also found in healthy controls. In addition, six previously reported single nucleotide polymorphisms (p.R48G, p.A119S, p.V243V, p.V432L, p.D449D, p.N453S) were also observed in POAG patients and controls, and they showed no obvious frequency difference between patients and controls.
This study provides a mutation spectrum of CYP1B1 resulting in POAG development in a Chinese population, which may demonstrate an involvement of the gene in a proportion of subjects with POAG and help to improve our understanding of the pathogenesis of CYP1B1-associated POAG.
CYP1B1基因已被证明与原发性开角型青光眼（POAG）相关。本研究旨在确定中国POAG患者中CYP1B1的突变谱。
本研究纳入了416例经标准眼科检查诊断为POAG的无亲缘关系病例，以及657例中国人群中的无亲缘关系健康对照。从所有参与者的外周血中收集基因组DNA。通过PCR从基因组DNA中扩增CYP1B1的编码序列，随后进行直接DNA测序。
在416例POAG患者中，25例患者检测到13个错义突变，包括9个已报道的突变和4个新突变（p.P93S、p.R259C、p.A295T、p.L475P）。所有这些突变均为杂合子，且已报道的突变先前在原发性先天性青光眼和/或POAG患者中发现。其中3个突变（p.L107V、p.E229K、p.V320L）在健康对照中也有发现。此外，在POAG患者和对照中还观察到6个先前报道的单核苷酸多态性（p.R48G、p.A119S、p.V243V、p.V432L、p.D449D、p.N453S），它们在患者和对照之间没有明显的频率差异。
本研究提供了中国人群中导致POAG发生的CYP1B1突变谱，这可能表明该基因在一部分POAG患者中起作用，并有助于提高我们对CYP1B1相关POAG发病机制的理解。
