Haplotypes in the complement factor H (CFH) gene: associations with drusen and advanced age-related macular degeneration.
Haplotypes in the complement factor H (CFH) gene: associations with drusen and advanced age-related macular degeneration.
复制标题
DOI：
10.1371/journal.pone.0001197
复制
发表时间：
2007-11-28
期刊：
影响因子：
3.7
通讯作者：
Klein ML
中科院分区：
文献类型：
--
作者：
Francis PJ;Schultz DW;Hamon S;Ott J;Weleber RG;Klein ML
视网膜相关性黄斑变性（AMD）是西方世界失明的主要原因，是一种影响50岁以上人群的复杂疾病。补体因子H（CFH）基因已被反复证明是决定对晚期形式的疾病易感性的主要因素。我们的目的是更好地了解该基因在AMD疾病过程中的功能作用，并评估它是否与早期疾病有关。我们在三个独立的AMD人群中对CFH基因位点的SNPs进行了基因分型：（a）至少有3名家庭成员患有AMD的大家庭;（B）晚期AMD的散发病例和（c）来自AMD相关眼病研究（AREDS）的病例。我们研究了CFH基因及其周围的多态性和单倍型，以评估它们在AMD中的作用。在家族性和散发性病例中，CFH与早期/中期和晚期AMD相关。在我们的人群中，CFH SNP rs 2274700与AMD的相关性最强，当与Y 402 H SNP和rs 1061147整合到一个单倍型中时，观察到最强的相关性（p<10−9）。我们的研究结果在三个代表AMD病例谱的人群中重现，提供了CFH基因与玻璃疣以及晚期AMD相关的证据。我们还在AMD人群中鉴定了新的易感性和保护性单倍型。
Age-related macular degeneration (AMD), the leading cause of blindness in the Western world, is a complex disease that affects people over 50 years old. The complement factor H (CFH) gene has been repeatedly shown to be a major factor in determining susceptibility to the advanced form of the condition. We aimed to better understand the functional role of this gene in the AMD disease process and assess whether it is associated with earlier forms of the disease. We genotyped SNPs at the CFH gene locus in three independent populations with AMD: (a) extended families where at least 3 family members had AMD; (b) sporadic cases of advanced AMD and (c) cases from the Age-Related Eye Disease Study (AREDS). We investigated polymorphisms and haplotypes in and around the CFH gene to assess their role in AMD. CFH is associated with early/intermediate and advanced AMD in both familial and sporadic cases. In our populations, the CFH SNP, rs2274700, is most strongly associated with AMD and when incorporated into a haplotype with the Y402H SNP and rs1061147, the strongest association is observed (p<10−9). Our results, reproduced in three populations that represent the spectrum of AMD cases, provide evidence that the CFH gene is associated with drusen as well as with advanced AMD. We also identified novel susceptibility and protective haplotypes in the AMD populations.