与年龄相关的黄斑变性、息肉状脉络膜血管病变和视网膜血管瘤样增生中 CFH 和 ARMS2 的变异。

CFH and ARMS2 variations in age-related macular degeneration, polypoidal choroidal vasculopathy, and retinal angiomatous proliferation.

机构信息

Department of Ophthalmology and Visual Sciences, Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.

出版信息

Invest Ophthalmol Vis Sci. 2010 Nov;51(11):5914-9. doi: 10.1167/iovs.10-5554. Epub 2010 Jun 23.

DOI:10.1167/iovs.10-5554

PMID:20574013

Abstract

PURPOSE

To seek an association in Japanese individuals between the CFH polymorphisms Y402H and I62V and the ARMS2 polymorphism A69S and age-related macular degeneration (AMD) or its three subtypes: typical (t)AMD, polypoidal choroidal vasculopathy (PCV), and retinal angiomatous proliferation (RAP).

METHODS

The three polymorphisms were genotyped in a case-control study of 1351 control subjects and 962 patients with AMD.

RESULTS

The three polymorphisms correlated with AMD (Y402H, P = 1.54 × 10(-6); I62V, P =1.94 × 10(-29); and A69S, P = 9.56 × 10(-43)). The I62V and A69S polymorphisms were associated with all three subtypes: tAMD (P = 3.74 × 10(-18) and 1.37 × 10(-35), respectively), PCV (P = 3.18 × 10(-19) and 3.96 × 10(-18), respectively), and RAP (P = 0.034 and 2.49 × 10(-18), respectively). Y402H was associated with tAMD (P = 3.00 × 10(-5)) and with PCV (P = 9.73 × 10(-5)), but no association was found with RAP, possibly because of the small sample size and the rare minor allele. The risk allele contribution of A69S was stronger for RAP than for tAMD or PCV and was stronger for tAMD than for PCV.

CONCLUSIONS

CFH Y402H is associated with AMD, tAMD, and PCV, whereas I62V is associated with all three subtypes. ARMS2 A69S has a strong association with all three subtypes, with the association being strongest for RAP and weakest for PCV. PCV and RAP may thus be subtypes of AMD that are genetically distinct from tAMD.

摘要

目的

在日本人群中，寻找 CFH 多态性 Y402H 和 I62V 与 ARMS2 多态性 A69S 与年龄相关性黄斑变性（AMD）或其三种亚型（典型 AMD、息肉样脉络膜血管病变（PCV）和视网膜血管瘤样增生（RAP））之间的关联。

方法

在一项针对 1351 名对照者和 962 名 AMD 患者的病例对照研究中，对这三种多态性进行了基因分型。

结果

这三种多态性与 AMD 相关（Y402H，P=1.54×10(-6)；I62V，P=1.94×10(-29)；A69S，P=9.56×10(-43)）。I62V 和 A69S 多态性与所有三种亚型均相关：tAMD（P=3.74×10(-18)和 1.37×10(-35)）、PCV（P=3.18×10(-19)和 3.96×10(-18)）和 RAP（P=0.034 和 2.49×10(-18)）。Y402H 与 tAMD（P=3.00×10(-5)）和 PCV（P=9.73×10(-5)）相关，但与 RAP 无关，这可能是由于样本量小和罕见的次要等位基因所致。与 tAMD 或 PCV 相比，RAP 中 A69S 的风险等位基因贡献更强，与 tAMD 相比，PCV 中 A69S 的风险等位基因贡献更强。