A common CFH haplotype, with deletion of CFHR1 and CFHR3, is associated with lower risk of age-related macular degeneration
A common CFH haplotype, with deletion of CFHR1 and CFHR3, is associated with lower risk of age-related macular degeneration
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DOI：
10.1038/ng1890
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发表时间：
2006-10-01
期刊：
影响因子：
30.8
通讯作者：
Chakravarthy, Usha
中科院分区：
文献类型：
--
作者：
Hughes, Anne E.;Orr, Nick;Chakravarthy, Usha
老年性黄斑变性（老年性黄斑变性，omim# 603075）是老年人视力损害的最常见原因，在75岁以上的欧洲人后裔中，有近10%患有严重疾病。这是一种复杂的疾病，遗传和环境因素对易感性有影响。补体因子H （CFH）最近被确定为AMD的主要易感基因，Y402H多态性被认为是可能的致病因素。研究人员对173例重度血管性AMD患者和170例无AMD症状的老年对照者进行了基因分型，分析了染色体1q23上CFH和5个CFH相关基因簇的多态性。详细分析显示，与AMD风险降低相关的常见单倍型存在于对照组的20%染色体和AMD个体的8%染色体上。我们发现该单倍型携带CFHR1和CFHR3的缺失，并且这些基因编码的蛋白在纯合子血清中缺失。缺失单倍型的保护作用不能归因于与Y402H的连锁不平衡，并在一个独立的样本中复制。
Age-related macular degeneration (AMD; OMIM #603075) is the most frequent cause of visual impairment in the elderly population, with severe disease affecting nearly 10% of individuals of European descent over the age of 75 years. It is a complex disease in which genetic and environmental factors contribute to susceptibility. Complement factor H (CFH) has recently been identified as a major AMD susceptibility gene, and the Y402H polymorphism has been proposed as the likely causative factor. We genotyped polymorphisms spanning the cluster of CFH and five CFH-related genes on chromosome 1q23 in 173 individuals with severe neovascular AMD and 170 elderly controls with no signs of AMD. Detailed analysis showed a common haplotype associated with decreased risk of AMD that was present on 20% of chromosomes of controls and 8% of chromosomes of individuals with AMD. We found that this haplotype carried a deletion of CFHR1 and CFHR3, and the proteins encoded by these genes were absent in serum of homozygotes. The protective effect of the deletion haplotype cannot be attributed to linkage disequilibrium with Y402H and was replicated in an independent sample.