Grassi Michael A, Fingert John H, Scheetz Todd E, Roos Benjamin R, Ritch Robert, West Sheila K, Kawase Kazuhide, Shire Abdirashid M, Mullins Robert F, Stone Edwin M
Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City 52242, USA.
Hum Mutat. 2006 Sep;27(9):921-5. doi: 10.1002/humu.20359.
Age-related macular degeneration (AMD) is the most common cause of irreversible visual loss in the developed world. Previous studies have demonstrated that the c.1204T>C, p.Tyr402His allelic variant in the complement factor H (CFH) gene is associated with an approximately three-fold increased risk for AMD in Caucasians of predominantly European descent. Both the prevalence as well as the phenotypic spectrum of AMD varies widely among persons of different ethnicities. We hypothesized that populations with a lower prevalence of AMD might also have a lower prevalence of the CFH risk allele. In this study we sought to determine the frequency of this sequence variant in control populations of Caucasians, African Americans, Hispanics, Somalis, and Japanese. Normal control populations were assembled for each ethnic group: Caucasian (n=148), Somali (n=128), African American (n=75), Hispanic (n=81), and Japanese (n=82). Individuals were genotyped using a restriction digest assay and the frequency of the C allele at nucleotide position 1204 of the CFH gene was determined. A bioinformatic approach was used to identify SNPs in linkage disequilibrium with rs1061170 (c.1204T>C, p.Tyr402His) from the human haplotype map project database (HapMap) in order to validate the findings. We found widely discordant frequencies of the risk allele between some of the different ethnic groups: Japanese 0.07+/-0.02, Hispanics 0.17+/-0.03, African-Americans 0.35+/-0.04, Caucasians 0.34+/-0.03, and Somalis 0.34+/-0.03. Allele frequencies generated by analysis of the HapMap database were consistent with these findings. This study suggests that there are other yet unidentified genetic factors important in the pathogenesis of AMD that may mitigate the effects of c.1204T>C, p.Tyr402His variant.
年龄相关性黄斑变性（AMD）是发达国家不可逆视力丧失的最常见原因。先前的研究表明，补体因子H（CFH）基因中的c.1204T>C、p.Tyr402His等位基因变体与主要为欧洲血统的白种人中患AMD的风险增加约三倍相关。AMD的患病率和表型谱在不同种族人群中差异很大。我们推测，AMD患病率较低的人群中CFH风险等位基因的患病率可能也较低。在本研究中，我们试图确定该序列变体在白种人、非裔美国人、西班牙裔、索马里人和日本人的对照人群中的频率。为每个种族群体组建了正常对照人群：白种人（n = 148）、索马里人（n = 128）、非裔美国人（n = 75）、西班牙裔（n = 81）和日本人（n = 82）。使用限制性消化分析法对个体进行基因分型，并确定CFH基因第1204位核苷酸处C等位基因的频率。采用生物信息学方法从人类单倍型图谱项目数据库（HapMap）中识别与rs1061170（c.1204T>C，p.Tyr402His）处于连锁不平衡的单核苷酸多态性（SNP），以验证研究结果。我们发现一些不同种族群体之间风险等位基因的频率差异很大：日本人0.07±0.02，西班牙裔0.17±0.03，非裔美国人0.35±0.04，白种人0.34±0.03，索马里人0.34±0.03。通过分析HapMap数据库产生的等位基因频率与这些结果一致。这项研究表明，在AMD发病机制中还有其他尚未确定的重要遗传因素，可能会减轻c.1204T>C、p.Tyr402His变体的影响。
