Silveira Alexandra C, Morrison Margaux A, Ji Fei, Xu Haiyan, Reinecke James B, Adams Scott M, Arneberg Trevor M, Janssian Maria, Lee Joo-Eun, Yuan Yang, Schaumberg Debra A, Kotoula Maria G, Tsironi Evangeline E, Tsiloulis Aristoteles N, Chatzoulis Dimitrios Z, Miller Joan W, Kim Ivana K, Hageman Gregory S, Farrer Lindsay A, Haider Neena B, DeAngelis Margaret M
Ocular Molecular Genetics Institute and Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA, USA.
Vision Res. 2010 Mar 31;50(7):698-715. doi: 10.1016/j.visres.2009.09.016. Epub 2009 Sep 26.
To identify novel genes and pathways associated with AMD, we performed microarray gene expression and linkage analysis which implicated the candidate gene, retinoic acid receptor-related orphan receptor alpha (RORA, 15q). Subsequent genotyping of 159 RORA single nucleotide polymorphisms (SNPs) in a family-based cohort, followed by replication in an unrelated case-control cohort, demonstrated that SNPs and haplotypes located in intron 1 were significantly associated with neovascular AMD risk in both cohorts. This is the first report demonstrating a possible role for RORA, a receptor for cholesterol, in the pathophysiology of AMD. Moreover, we found a significant interaction between RORA and the ARMS2/HTRA1 locus suggesting a novel pathway underlying AMD pathophysiology.
为了鉴定与年龄相关性黄斑变性（AMD）相关的新基因和通路，我们进行了微阵列基因表达和连锁分析，结果表明候选基因维甲酸受体相关孤儿受体α（RORA，位于15号染色体长臂）具有相关性。随后，我们在一个基于家系的队列中对159个RORA单核苷酸多态性（SNP）进行了基因分型，并在一个非亲缘的病例对照队列中进行了重复验证，结果表明位于内含子1中的SNP和单倍型在两个队列中均与新生血管性AMD风险显著相关。这是首份证明胆固醇受体RORA在AMD病理生理学中可能发挥作用的报告。此外，我们发现RORA与ARMS2/HTRA1基因座之间存在显著相互作用，提示AMD病理生理学存在一条新的通路。
