Rohrer Bärbel, Frazer-Abel Ashley, Leonard Anthony, Ratnapriya Rinki, Ward Tyson, Pietraszkiewicz Alexandra, O'Quinn Elizabeth, Adams Katherine, Swaroop Anand, Wolf Bethany Jacobs
Department of Ophthalmology, Medical University of South Carolina, Charleston, SC.
Department of Neuroscience, Medical University of South Carolina, Charleston, SC.
Mol Vis. 2019 Feb 8;25:79-92. eCollection 2019.
Smoking and the incidence of age-related macular degeneration (AMD) have been linked to an overactive complement system. Here, we examined in a retrospective cohort study whether AMD-associated single nucleotide polymorphisms (SNPs), smoking, ethnicity, and disease status are correlated with blood complement levels.
: The study involved 91 AMD patients and 133 controls, which included 73% Americans of European descent (EUR) and 27% Americans of African descent (AFR) in South Carolina. : Participants were genotyped for 10 SNPs and systemic levels of complement factor H (CFH) activity, and the complement activation products C3a, C5a, and Bb were assessed. : Univariate and multivariable logistic regression models were used to examine associations between AMD status and distinct readouts.
AMD affects EUR individuals more than AFRs. EUR but not AFR AMD subjects revealed higher levels of Factors C3a and Bb. In all subjects, a 10-unit increase in C3a levels was associated with an approximately 10% increase in the odds of being AMD-positive, and C3a and Bb were associated with smoking. While CFH activity levels were not correlated with AMD, a significant interaction was evident between patient age and CFH activity. Finally, EURs had lower odds of AMD with enhanced copies of rs1536304 () and higher odds with more copy numbers of rs3766404 ().
Our results support previous studies of systemic complement components being potential biomarkers for AMD, but they suggest that smoking and disease do not synergistically affect complement levels. We also suggest a novel susceptibility and protective haplotypes in the South Carolinian AMD population. Our studies indicate that augmented complement activation associated with advanced AMD could be attributed to a decrease in CFH activity in younger patients.
吸烟与年龄相关性黄斑变性（AMD）的发病率与补体系统过度活跃有关。在此，我们在一项回顾性队列研究中检查了AMD相关单核苷酸多态性（SNP）、吸烟、种族和疾病状态是否与血液补体水平相关。
该研究纳入了91名AMD患者和133名对照，其中包括南卡罗来纳州73%的欧洲裔美国人（EUR）和27%的非洲裔美国人（AFR）。对参与者进行10个SNP的基因分型，并评估补体因子H（CFH）活性的全身水平以及补体激活产物C3a、C5a和Bb。使用单变量和多变量逻辑回归模型检查AMD状态与不同读数之间的关联。
AMD对EUR个体的影响大于AFR个体。EUR但不是AFR AMD受试者显示出较高水平的C3a因子和Bb。在所有受试者中，C3a水平每增加10个单位，AMD阳性几率约增加10%，并且C3a和Bb与吸烟有关。虽然CFH活性水平与AMD无关，但患者年龄与CFH活性之间存在明显的相互作用。最后，rs1536304（）拷贝数增加的EUR患AMD的几率较低，而rs3766404拷贝数更多的EUR患AMD的几率较高。
我们的结果支持先前关于全身补体成分是AMD潜在生物标志物的研究，但表明吸烟和疾病不会协同影响补体水平。我们还在南卡罗来纳州AMD人群中提出了新的易感和保护单倍型。我们的研究表明，与晚期AMD相关的补体激活增强可能归因于年轻患者CFH活性的降低。
