Li Mingyao, Atmaca-Sonmez Pelin, Othman Mohammad, Branham Kari E H, Khanna Ritu, Wade Michael S, Li Yun, Liang Liming, Zareparsi Sepideh, Swaroop Anand, Abecasis Gonçalo R
Department of Biostatistics, 1420 Washington Heights, University of Michigan, Ann Arbor, Michigan 48109, USA.
Nat Genet. 2006 Sep;38(9):1049-54. doi: 10.1038/ng1871. Epub 2006 Aug 27.
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.
在发达国家，年龄相关性黄斑变性是老年人失明的常见原因。补体因子H（CFH）中编码序列变异Y402H的一种常见多态性与疾病易感性密切相关。在此，我们检测了726名受影响个体（包括544名无亲缘关系个体）和268名无亲缘关系对照中CFH及其周围的84种多态性。在这个样本中，其中20种多态性与疾病易感性的关联比Y402H变异更强。此外，没有单一多态性能够解释CFH基因座对疾病易感性的影响。相反，多种多态性定义了一组四种常见单倍型（其中两种与疾病易感性相关，两种似乎具有保护作用）以及多种罕见单倍型（总体上与易感性增加相关）。我们的结果表明该区域存在多个疾病易感等位基因，并且非编码CFH变异在疾病易感性中起作用。
