Klein Ronald, Knudtson Michael D, Klein Barbara E K, Wong Tien Y, Cotch Mary Frances, Liu Kiang, Cheng Ching Y, Burke Gregory L, Saad Mohammed F, Jacobs David R, Sharrett A Richey
Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53726-2397, USA.
Ophthalmology. 2008 Oct;115(10):1742-9. doi: 10.1016/j.ophtha.2008.03.021. Epub 2008 Jun 5.
To describe the relationship of systemic inflammatory disease, complement factor H (CFH) Y402H (1277T-->C) genotype status and age-related macular degeneration (AMD) prevalence in a multiethnic population of whites, blacks, Hispanics, and Chinese.
Population-based, cross-sectional study.
We included 5887 persons aged 45 to 84 years with gradable AMD.
Digital fundus photographs were used to measure AMD. Two years earlier, biomarkers of inflammation were measured and history of inflammatory disease and use of antiinflammatory agents obtained.
Prevalence of AMD.
While controlling for age, gender, race/ethnicity, and study site, there were no associations between systemic inflammatory factors and AMD severity. Higher levels of high-sensitivity C-reactive protein (odds ratio [OR] per standard deviation [SD] increase in natural log [ln] units, 2.34; 95% confidence interval [CI], 1.33-4.13) and interleukin-6 (OR per SD in ln, 2.06; 95% CI, 1.21-3.49) were associated with geographic atrophy but not other AMD end points. History of periodontal disease (OR, 1.68; 95% CI, 1.14-2.47) was related to increased retinal pigment. A history of arthritis was associated with soft distinct drusen (OR, 1.24; 95% CI, 1.06-1.46). A history of oral steroid use was related to large drusen (OR, 2.13; 95% CI, 1.14-3.97) and soft distinct drusen (OR, 1.76; 95% CI, 1.00-3.10) and history of cyclooxygenase 2 inhibitor use were associated with large drusen (OR, 1.50; 95% CI, 1.10-2.04), soft indistinct drusen (OR, 1.84; 95% CI, 1.09-3.10), and large drusen area (OR, 1.66; 95% CI, 1.02-2.71). Whites, blacks, and Hispanics with CFH Y402H CC variant genotype had the highest frequency of early AMD compared with those with wild TT genotype. The frequency of CFH did explain some of the difference in AMD prevalence between Chinese and Hispanics compared with whites, but did not explain the difference in prevalence between whites and blacks.
This study confirmed associations of the Y402H CFH gene variant with AMD in nonwhite populations, but neither explained the lack of association between inflammatory factors and AMD in the cohort nor the basis for the observed differences in AMD prevalence across ethnic groups.
描述白人、黑人、西班牙裔和华裔多民族人群中全身炎症性疾病、补体因子H（CFH）Y402H（1277T→C）基因型状态与年龄相关性黄斑变性（AMD）患病率之间的关系。
基于人群的横断面研究。
我们纳入了5887名年龄在45至84岁之间且患有可分级AMD的人。
使用数字眼底照片测量AMD。两年前，测量炎症生物标志物，获取炎症性疾病病史和抗炎药物使用情况。
AMD患病率。
在控制年龄、性别、种族/民族和研究地点后，全身炎症因子与AMD严重程度之间无关联。高敏C反应蛋白水平较高（每标准差[SD]自然对数[ln]单位增加的比值比[OR]为2.34；95%置信区间[CI]为1.33 - 4.13）和白细胞介素-6（每SD的ln的OR为2.06；95%CI为1.21 - 3.49）与地图样萎缩相关，但与其他AMD终点无关。牙周疾病史（OR为1.68；95%CI为1.14 - 2.47）与视网膜色素增加有关。关节炎病史与软性边界清晰的玻璃膜疣相关（OR为1.24；95%CI为1.06 - 1.46）。口服类固醇药物史与大玻璃膜疣（OR为2.13；95%CI为1.14 - 3.97）和软性边界清晰的玻璃膜疣（OR为1.76；95%CI为1.00 - 3.10）相关，使用环氧化酶2抑制剂史与大玻璃膜疣（OR为1.50；95%CI为1.10 - 2.04）、软性边界不清晰的玻璃膜疣（OR为1.84；95%CI为1.09 - 3.10）和大玻璃膜疣面积（OR为1.66；95%CI为1.02 - 2.71）相关。与野生型TT基因型相比，携带CFH Y402H CC变异基因型的白人、黑人和西班牙裔早期AMD的频率最高。CFH的频率确实解释了与白人相比华裔和西班牙裔之间AMD患病率差异的一部分，但没有解释白人和黑人之间患病率的差异。
本研究证实了Y402H CFH基因变异与非白人人群中AMD的关联，但既未解释该队列中炎症因子与AMD之间缺乏关联的原因，也未解释观察到的不同种族间AMD患病率差异的基础。
