Mutation spectrum of CYP1B1 in Chinese patients with primary open-angle glaucoma
Mutation spectrum of CYP1B1 in Chinese patients with primary open-angle glaucoma
复制标题
中国原发性开角型青光眼患者CYP1B1突变谱
DOI：
10.1136/bjophthalmol-2014-306054
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发表时间：
2015-03-01
影响因子：
4.1
通讯作者：
Yang, Zhenglin
中科院分区：
文献类型：
--
作者：
Gong, Bo;Qu, Chao;Yang, Zhenglin
目的CYP 1B 1基因与原发性开角型青光眼（primary open-angle glaucoma，POAG）有关。本研究的目的是确定CYP 1B 1在中国POAG患者中的突变谱。方法对416例经标准眼科检查确诊的原发性开角型青光眼患者和657例正常对照者进行研究。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CYP 1B 1的编码序列，随后进行直接DNA测序。结果416例原发性开角型青光眼患者中，25例患者共检测到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，并且先前已在原发性先天性青光眼和/或POAG患者中发现了报告的突变。其中3株（p.L107V、p.E229K、p.V320L）在健康对照中也有表达。此外，在POAG患者和对照组中还发现了6个已报道的单核苷酸多态性位点（p.R48G、p.A119S、p.V243V、p.V432L、p.D449D、p.N453S），且在POAG患者和对照组中的频率无明显差异。结论本研究提供了导致中国人群POAG发生的CYP 1B 1基因突变谱，可能在一定比例的POAG患者中存在该基因的参与，有助于提高对CYP 1B 1相关POAG发病机制的认识。
Purpose 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. Methods 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. Results 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. Conclusions 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.