CFH haplotypes without the Y402H coding variant show strong association with susceptibility to age-related macular degeneration
CFH haplotypes without the Y402H coding variant show strong association with susceptibility to age-related macular degeneration
复制标题
DOI：
10.1038/ng1871
复制
发表时间：
2006-09-01
期刊：
影响因子：
30.8
通讯作者：
Abecasis, Goncalo R.
中科院分区：
文献类型：
--
作者：
Li, Mingyao;Atmaca-Sonmez, Pelin;Abecasis, Goncalo R.
在发达国家，老年性黄斑变性是老年人致盲的常见原因。一种常见的编码补体因子H(CFH)序列变异Y402H的多态与疾病易感性密切相关。在这里，我们研究了726名患病个体(包括544名无关个体)和268名无关对照中CFH及其周围84个基因的多态性。在这个样本中，这些多态中的20个与疾病易感性的相关性比Y402H变异更强。此外，没有单一的多态可以解释CFH基因座对疾病易感性的贡献。相反，多重多态性定义了一组四种常见的单倍型(其中两种与疾病易感性相关，两种似乎具有保护性)和多种稀有单倍型(与总体上增加的易感性相关)。我们的结果表明，该区域存在多个疾病易感等位基因，非编码CFH变异在疾病易感性中起作用。
In developed countries, age-related macular degeneration is a common cause of blindness in the elderly. A common polymorphism, encoding the sequence variation Y402H in complement factor H (CFH), has been strongly associated with disease susceptibility. Here, we examined 84 polymorphisms in and around CFH in 726 affected individuals (including 544 unrelated individuals) and 268 unrelated controls. In this sample, 20 of these polymorphisms showed stronger association with disease susceptibility than the Y402H variant. Further, no single polymorphism could account for the contribution of the CFH locus to disease susceptibility. Instead, multiple polymorphisms defined a set of four common haplotypes (of which two were associated with disease susceptibility and two seemed to be protective) and multiple rare haplotypes (associated with increased susceptibility in aggregate). Our results suggest that there are multiple disease susceptibility alleles in the region and that noncoding CFH variants play a role in disease susceptibility.