Department of Neurology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
PLoS One. 2013 Jul 29;8(7):e70193. doi: 10.1371/journal.pone.0070193. Print 2013.
The purpose of the study was to determine serum complement factor H (CFH) levels in patients of age related macular degeneration (AMD) and examine its association with CFH Y402H polymorphism. 115 AMD patients and 61 normal controls were recruited in this study. The single nucleotide polymorphism was assayed by real time PCR and serum CFH levels were measured by ELISA and standardized to total serum protein. Chi-square test was applied to polymorphism analysis while Mann Whitney U-statistic for CFH-levels. Mendelian randomization approach was used for determining causal relationship. The genotype frequency differed between the AMD patients (TT- 18.3%, TC-41.3% and CC-40.4%) and controls (TT-76.3%, TC-13.6%, and CC-10.1%) (p = 0001). The frequency of alleles was also significantly different when AMD (T-39% and C-61%) was compared to controls (T-83% and C-17%) (p = 0.0001). Level of serum CFH was significantly lower in AMD patients as compared to normal controls (p = 0.001). Our data showed that the CFH Y402H polymorphism is a risk factor for AMD in the North Indian population. Mendelian randomization approach revealed that CFH Y402H polymorphism affects AMD risk through the modification of CFH serum levels.
本研究旨在测定年龄相关性黄斑变性（AMD）患者血清补体因子 H（CFH）水平，并探讨其与 CFH Y402H 多态性的关系。本研究纳入了 115 名 AMD 患者和 61 名正常对照。采用实时 PCR 法检测单核苷酸多态性，ELISA 法测定血清 CFH 水平，并标准化为总血清蛋白。采用卡方检验进行多态性分析，Mann-Whitney U 检验进行 CFH 水平分析。采用孟德尔随机化方法确定因果关系。AMD 患者（TT-18.3%，TC-41.3%和 CC-40.4%）和对照组（TT-76.3%，TC-13.6%和 CC-10.1%）的基因型频率存在差异（p=0.0001）。AMD 组（T-39%和 C-61%）和对照组（T-83%和 C-17%）的等位基因频率也存在显著差异（p=0.0001）。与正常对照组相比，AMD 患者血清 CFH 水平明显降低（p=0.001）。我们的数据表明，CFH Y402H 多态性是北印度人群 AMD 的危险因素。孟德尔随机化方法表明，CFH Y402H 多态性通过 CFH 血清水平的改变影响 AMD 的发病风险。
