Park Soo, Jamshidi Yalda, Vaideanu Daniela, Bitner-Glindzicz Maria, Fraser Scott, Sowden Jane C
Developmental Biology Unit, University College London Institute of Child Health and Great Ormond Street Hospital for Children NHS Trust, London, United Kingdom.
Invest Ophthalmol Vis Sci. 2009 Apr;50(4):1522-30. doi: 10.1167/iovs.08-2483. Epub 2008 Oct 24.
Primary open-angle glaucoma (POAG) is a common disease requiring early diagnosis and treatment to avoid asymptomatic visual field loss and eventual blindness. LMX1B mutations cause dominantly-inherited Nail-Patella syndrome in which approximately 33% of patients develop glaucoma. This study investigated the wider role of LMX1B in POAG.
The contribution of variation at the LMXIB locus to risk of glaucoma was investigated in a case-control genetic association study in 272 patients with high-tension glaucoma (HTG), 37 patients with normal-tension glaucoma (NTG), 58 patients with ocular hypertension (OHT), and 276 controls.
Significant SNP associations were found for each patient group: rs7859156 was associated with HTG (P=0.0015; odds ratio [OR], 0.64) and OHT (P=0.0482; OR, 0.59); rs7854658 was associated with NTG (P=0.0041; OR, 0.30). A protective ATG haplotype (including rs7859156) was less prevalent in patients with raised intraocular pressure (22.7% in combined HTG+OHT group vs. 31.7% in controls; P=0.0005), and in patients with glaucoma (22.9% in combined HTG+NTG group vs. 31.7% in controls; P=0.0008). ATG carriers in these combined groups had a decreased risk of developing glaucoma (OR, 0.72 and OR, 0.73, respectively). A GCAGAC haplotype (including rs7854658) was also less prevalent in glaucoma patients (16.5% vs. 24.7%; P=0.0005) and carriers had a decreased risk of developing glaucoma (OR, 0.70).
LMX1B haplotypes influence susceptibility to glaucoma in the general population, suggesting altered LMX1B function predisposes to glaucomatous damage and that this role may be independent of raised intraocular pressure.
原发性开角型青光眼（POAG）是一种常见疾病，需要早期诊断和治疗以避免无症状性视野缺损及最终失明。LMX1B突变会导致显性遗传的指甲-髌骨综合征，其中约33%的患者会患上青光眼。本研究调查了LMX1B在POAG中更广泛的作用。
在一项病例对照基因关联研究中，对272例高眼压性青光眼（HTG）患者、37例正常眼压性青光眼（NTG）患者、58例高眼压症（OHT）患者和276例对照进行研究，以调查LMXIB基因座变异对青光眼风险的影响。
在每个患者组中均发现了显著的单核苷酸多态性（SNP）关联：rs7859156与HTG相关（P=0.0015；优势比[OR]，0.64）和OHT相关（P=0.0482；OR，0.59）；rs7854658与NTG相关（P=0.0041；OR，0.30）。一种保护性的ATG单倍型（包括rs7859156）在眼压升高的患者中不太常见（HTG+OHT联合组中为22.7%，对照组中为31.7%；P=0.0005），在青光眼患者中也不太常见（HTG+NTG联合组中为22.9%，对照组中为31.7%；P=0.0008）。这些联合组中的ATG携带者患青光眼的风险降低（OR分别为0.72和0.73）。一种GCAGAC单倍型（包括rs7854658）在青光眼患者中也不太常见（16.5%对24.7%；P=0.0005），携带者患青光眼的风险降低（OR，0.70）。
LMX1B单倍型影响普通人群对青光眼的易感性，提示LMX1B功能改变易导致青光眼性损害，且该作用可能独立于眼压升高。
