van de Ven Johannes P H, Smailhodzic Dženita, Boon Camiel J F, Fauser Sascha, Groenewoud Joannes M M, Chong N Victor, Hoyng Carel B, Klevering B Jeroen, den Hollander Anneke I
Department of Ophthalmology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.
Mol Vis. 2012;18:2271-8. Epub 2012 Aug 18.
To assess the association of gender, cigarette smoking, body-mass index, and nine genetic risk variants with cuticular drusen (CD), a well recognized subtype of age-related macular degeneration (AMD).
A total of 757 patients with AMD, including 217 patients with CD, and 553 control individuals were interviewed with a questionnaire and underwent an ophthalmic examination. Venous blood samples were obtained for genomic DNA extraction, and genotyping was performed of single nucleotide polymorphisms previously associated with AMD. Odds ratios were calculated for patients with CD, using unaffected control individuals as a reference. Furthermore, odds ratios in patients with CD were compared to those in patients with "non-CD" AMD.
The CD subtype of AMD was significantly associated with current smoking as well as variants in the complement factor H (CFH), age-related maculopathy susceptibility 2 (ARMS2), complement factor B/complement component 2 (CFB/C2), complement component 3 (C3), and apolipoprotein E (APOE) genes. In patients with CD, the association with the CFH Y402H risk allele was significantly higher (p=0.022), whereas the association with current smoking was significantly lower (p<0.001) than in the heterogeneous group of patients with "non-CD" AMD.
The AMD subtype of CD was associated with previously identified genetic AMD risk factors. However, the association with the CFH Y402H risk allele appeared to be stronger, whereas the association with smoking was less pronounced when compared to AMD as a whole. This study suggests a more important role for genetic factors than environmental factors in the development of this well defined subtype of AMD. These findings stress the importance of detailed phenotyping in AMD to identify homogeneous AMD subtypes, which may be associated with different risk factors and disease mechanisms. Such studies will improve the accuracy of predictive models and the effectiveness of preventive and therapeutic options in AMD.
评估性别、吸烟、体重指数以及九种基因风险变异与玻璃膜疣（CD）之间的关联，玻璃膜疣是年龄相关性黄斑变性（AMD）一种公认的亚型。
共对757例AMD患者（包括217例CD患者）和553名对照个体进行问卷调查并接受眼科检查。采集静脉血样本用于提取基因组DNA，并对先前与AMD相关的单核苷酸多态性进行基因分型。以未受影响的对照个体为参照，计算CD患者的比值比。此外，将CD患者的比值比与“非CD”型AMD患者的比值比进行比较。
AMD的CD亚型与当前吸烟以及补体因子H（CFH）、年龄相关性黄斑病变易感性2（ARMS2）、补体因子B/补体成分2（CFB/C2）、补体成分3（C3）和载脂蛋白E（APOE）基因的变异显著相关。在CD患者中，与CFH Y402H风险等位基因的关联显著更高（p = 0.022），而与当前吸烟的关联显著低于“非CD”型AMD患者的异质性组（p < 0.001）。
CD型AMD与先前确定的遗传性AMD风险因素相关。然而，与CFH Y402H风险等位基因的关联似乎更强，而与吸烟的关联与整体AMD相比则不太明显。这项研究表明，在这种明确的AMD亚型的发生发展中，遗传因素比环境因素起更重要的作用。这些发现强调了在AMD中进行详细表型分析以识别可能与不同风险因素和疾病机制相关的同质AMD亚型的重要性。此类研究将提高AMD预测模型的准确性以及预防和治疗方案的有效性。
