Genome-wide Association Study of Normal Tension Glaucoma: Common Variants in SRBD1 and ELOVL5 Contribute to Disease Susceptibility
Genome-wide Association Study of Normal Tension Glaucoma: Common Variants in SRBD1 and ELOVL5 Contribute to Disease Susceptibility
复制标题
DOI：
10.1016/j.ophtha.2009.12.001
复制
发表时间：
2010-07-01
期刊：
影响因子：
13.7
通讯作者：
Inoko, Hidetoshi
中科院分区：
文献类型：
--
作者：
Meguro, Akira;Inoko, Hidetoshi;Inoko, Hidetoshi
目的：导致正常眼压性青光眼（NTG）发展的因素尚未确定，NTG是以视网膜神经节细胞、视神经轴突和视野的进行性丧失为特征的退行性视神经病变。为了确定NTG的遗传危险因素，我们进行了NTG的全基因组关联研究。设计：病例对照研究。参与者：研究队列包括305名日本NTG患者和355名对照。方法：我们对500 568个单核苷酸多态性（SNP）进行基因分型，并评估病例和对照之间的等位基因多样性。主要结果测量：500 568个SNP的基因型。结果：NTG相关性最强的两个SNPs rs3213787和rs735860分别位于SRBD 1的内含子和SLVL 5的3 '非翻译区（P = 2.5 × 10（-9），比值比= 2.80和P = 4.1 × 10（-6），比值比= 1.69）。实时定量逆转录-聚合酶链反应分析显示，每个基因的表达显着增加，在白色血细胞中的受试者窝藏这些SNPs.Conclusions的风险等位基因：我们的全基因组关联研究确定SRBD 1和SRBD VL 5为NTG的新的易感基因。因为据报道SRBD 1和SRBD 5参与诱导细胞生长抑制或凋亡，SRBD 1和SRBD 5级联的调节可能在NTG发展的风险中发挥重要的生理作用。财务披露：作者对本文中讨论的任何材料没有专有或商业利益。Ophthalmology 2010; 117：1331-1338（C）2010，美国眼科学会。
Purpose: Factors contributing to the development of normal tension glaucoma (NTG), degenerative optic neuropathy characterized by the progressive loss of retinal ganglion cells, optic nerve axons, and visual fields, have not been determined. To identify genetic risk factors for NTG, we performed a genome-wide association study of NTG.Design: Case-control study.Participants: The study cohort consisted of 305 Japanese patients with NTG and 355 controls.Methods: We genotyped 500 568 single-nucleotide polymorphisms (SNPs) and assessed the allelic diversity among cases and controls.Main Outcome Measures: Genotypes of 500 568 SNPs.Results: The 2 most strongly NTG-associated SNPs, rs3213787 and rs735860, are located in an intron of SRBD1 and the 3'-untranslated region of ELOVL5 (P = 2.5X10(-9), odds ratio = 2.80 and P = 4.1X10(-6), odds ratio = 1.69), respectively. Real-time quantitative reverse transcription- polymerase chain reaction assays showed significantly increased expression of each gene in the white blood cells of subjects harboring the risk allele of these SNPs.Conclusions: Our genome-wide association study identified SRBD1 and ELOVL5 as new susceptibility genes for NTG. Because SRBD1 and ELOVL5 are reportedly involved in the induction of cell growth inhibition or apoptosis, the regulation of SRBD1 and ELOVL5 cascades may play an important physiologic role in the risk of NTG development.Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2010; 117: 1331-1338 (C) 2010 by the American Academy of Ophthalmology.