Faculté de Médecine Henri Mondor, Department of Ophthalmology, APHP (Assistance Publique Hôpitaux Paris), Groupe Hospitalier Albert Chenevier-Henri Mondor, University Paris 12, Créteil, France.
Invest Ophthalmol Vis Sci. 2010 May;51(5):2620-5. doi: 10.1167/iovs.09-4423. Epub 2009 Dec 30.
Major genetic risk factors have recently been identified for age-related macular degeneration (AMD), including the ARMS2/LOC387715 and CFH at-risk polymorphisms. The study was conducted to establish correlations between the AMD genotype and both the phenotype and severity of AMD.
In a prospective cohort of 1216 AMD patients, four genotypic homozygous groups were identified (n = 264): double homozygous for wild-type alleles (group 1, n = 49), homozygous for the at-risk allele of ARMS2/LOC387715 only (group 2, n = 57), homozygous for the at-risk allele of CFH only (group 3, n = 106), and double homozygous for both at-risk alleles (group 4, n = 52). The phenotypic classification of exudative AMD was based on fluorescein angiography.
Mean age at presentation was significantly lower in group 4 than in group 1 (P < 0.014). Patients in group 4 presented more often with bilateral CNV and fibrovascular scars than did patients in group 1 (P < 0.001 and < 0.0031 respectively) and with significantly lower visual acuity (VA) in the first affected eye than did patients in group 1 (P < 0.02). Patients in group 2 presented with worse VA than did patients in group 3 (P < 0.003). Classic CNV was more commonly associated with the at-risk allele of the ARMS2/LOC387715 locus than with the at-risk allele of the CFH gene (P < 0.026).
This study demonstrates an association between the at-risk allele of the ARMS2/LOC387715 locus and classic CNV, fibrovascular lesions, and poor VA. Individuals double homozygous for both at-risk alleles had a higher risk of being affected with a severe form of AMD at an earlier age.
最近已经确定了与年龄相关性黄斑变性（AMD）相关的主要遗传风险因素，包括 ARMS2/LOC387715 和 CFH 风险等位基因。本研究旨在建立 AMD 基因型与 AMD 的表型和严重程度之间的相关性。
在一项针对 1216 名 AMD 患者的前瞻性队列研究中，确定了四个纯合基因型组（n=264）：野生型等位基因的双重纯合子（组 1，n=49）、仅 ARMS2/LOC387715 风险等位基因的纯合子（组 2，n=57）、仅 CFH 风险等位基因的纯合子（组 3，n=106）以及两个风险等位基因的双重纯合子（组 4，n=52）。渗出性 AMD 的表型分类基于荧光素血管造影。
组 4 的发病年龄明显低于组 1（P<0.014）。组 4 的患者比组 1 的患者更常出现双侧 CNV 和纤维血管性瘢痕（P<0.001 和 P<0.0031），且第一只受影响的眼睛的视力（VA）明显低于组 1（P<0.02）。组 2 的患者比组 3 的患者的 VA 更差（P<0.003）。经典型 CNV 更常与 ARMS2/LOC387715 基因座的风险等位基因相关，而不是与 CFH 基因的风险等位基因相关（P<0.026）。
本研究表明 ARMS2/LOC387715 基因座的风险等位基因与经典型 CNV、纤维血管病变和低 VA 相关。两个风险等位基因的双重纯合子个体发生严重 AMD 的风险更高，且发病年龄更早。
