Seddon Johanna M, Reynolds Robyn, Rosner Bernard
Ophthalmic Epidemiology and Genetics Service, Department of Ophthalmology, Tufts University School of Medicine and Tufts Medical Center, New England Eye Center, Boston, Massachusetts 02111, USA.
Invest Ophthalmol Vis Sci. 2009 Feb;50(2):586-91. doi: 10.1167/iovs.08-2514. Epub 2008 Oct 20.
To evaluate the relationship between peripheral retinal drusen and reticular pigment changes and genotypes associated with age-related macular degeneration (AMD).
Using standard protocols, 2103 family members and twins were examined. Clinical and photographic data were graded according to the Clinical Age-Related Maculopathy Grading System (CARMS) as grade 1 (no AMD), grade 2 (small drusen and/or pigment irregularities), grade 3 (intermediate AMD), grade 4 (central or noncentral geographic atrophy), or grade 5 (neovascular disease). Peripheral drusen and reticular pigment were assessed with a standardized examination. Associations between six AMD genetic variants and retinal phenotypes were analyzed.
AMD grade was associated with peripheral drusen and reticular pigment (odds ratio [OR] 1.9 for advanced AMD; P<0.001). Both peripheral retinal phenotypes were associated with AMD related genotypes. For CFHY402H, the OR was 2.8 for the CC genotype versus TT (P for trend<0.001, with increase in peripheral drusen with each additional risk [C] allele). Similar results were seen for CFHrs1410996. Reticular pigment was related to CFHY402H, with OR 2.0 for the CC genotype versus TT (P for trend<0.001, for increase in pigment with each risk allele) and to CFHrs1410996 (P for trend=0.006). These findings were not seen for the LOC387715 A69S gene region, CFB, C2, or C3. Among individuals with no or minimal maculopathy, CFH variants were associated with more than a twofold increased risk of drusen and reticular pigment.
Peripheral retinal drusen and reticular pigment are associated with AMD and with CFHY402H and CFHrs1410996 genotypes, adjusting for AMD grade. These phenotypes may be a marker of genetic susceptibility for patients with or without AMD.
评估周边视网膜玻璃膜疣与网状色素改变以及与年龄相关性黄斑变性（AMD）相关的基因型之间的关系。
采用标准方案对2103名家庭成员和双胞胎进行检查。临床和摄影数据根据临床年龄相关性黄斑病变分级系统（CARMS）分为1级（无AMD）、2级（小玻璃膜疣和/或色素不规则）、3级（中度AMD）、4级（中心或非中心性地图样萎缩）或5级（新生血管疾病）。通过标准化检查评估周边玻璃膜疣和网状色素。分析六种AMD基因变异与视网膜表型之间的关联。
AMD分级与周边玻璃膜疣和网状色素相关（晚期AMD的优势比[OR]为1.9；P<0.001）。两种周边视网膜表型均与AMD相关基因型有关。对于CFHY402H，CC基因型与TT基因型相比，OR为2.8（趋势P<0.001，随着每个额外的风险[C]等位基因，周边玻璃膜疣增加）。CFHrs1D10996也有类似结果。网状色素与CFHY402H相关，CC基因型与TT基因型相比，OR为2.0（趋势P<0.001，随着每个风险等位基因色素增加），与CFHrs1410996相关（趋势P=0.006）。在LOC387715 A69S基因区域、CFB、C2或C3中未发现这些结果。在无或轻度黄斑病变的个体中，CFH变异与玻璃膜疣和网状色素风险增加两倍以上相关。
调整AMD分级后，周边视网膜玻璃膜疣和网状色素与AMD以及CFHY402H和CFHrs1410996基因型相关。这些表型可能是有或无AMD患者遗传易感性的标志物。
