Weger Martin, Renner Wilfried, Steinbrugger Iris, Köfer Katharina, Wedrich Andreas, Groselj-Strele Andrea, El-Shabrawi Yosuf, Schmut Otto, Haas Anton
Department of Ophthalmology, Medical University of Graz, Austria.
Mol Vis. 2007 Jul 24;13:1274-9.
Exudative age-related macular degeneration (AMD) is one of the most common causes of severe visual loss. Both environmental and genetic factors, such as the complement factor H (CFH) 402H allele, have been associated with AMD. Recently, the HTRA1 -625A allele was identified as a novel risk marker in both a North American and a Chinese population. The present study was performed to evaluate the association of the HTRA1 -625A allele with exudative AMD in a Central European population.
The present case-control study included 242 patients with exudative AMD and 157 control subjects. Genotypes of the HTRA1 -625G>A polymorphism were determined by a 5'-exonuclease assay (TaqMan). Determination of CFH Y402H genotypes was done by allele specific digestion of polymerase chain products.
Carriers of the HTRA1 -625AA genotype were found significantly more often in AMD patients than among control subjects (27.7% versus 5.1%; p<0.001). Binary logistic regression analysis binary logistic regression analysis revealed an odds ratio (OR) of 2.7 (95% confidence interval (CI): 1.1-6.8) for AMD among subjects heterozygous for the HTRA1 -625A allele compared to those with the wildtype genotype, when adjusted for CFH Y402H genotypes (p=0.034). The OR increased to 10.2 (95% CI: 3.0-34.5) among subjects homozygous for the HTRA1 -625A allele (p<0.001). The OR for AMD among heterozygous carriers of the CFH 402H variant was 3.6 (95% CI: 1.6-7.8) compared to those with the wildtype genotype, when adjusted for HTRA1 -625G>A genotypes (p=0.001). The OR increased to 9.8 (95% CI: 3.7-25.9) among subjects homozygous for the CFH 402HH genotype (p<0.001). Interaction terms between CFH and HTRA1 genotypes were not significantly associated with AMD.
Our data suggest that both the HTRA1 -625A allele and the CFH 402H allele are independently associated with exudative AMD in a Central European population.
渗出性年龄相关性黄斑变性（AMD）是严重视力丧失的最常见原因之一。环境和遗传因素，如补体因子H（CFH）402H等位基因，均与AMD有关。最近，HTRA1 -625A等位基因在北美和中国人群中均被鉴定为一种新的风险标志物。本研究旨在评估中欧人群中HTRA1 -625A等位基因与渗出性AMD的相关性。
本病例对照研究纳入了242例渗出性AMD患者和157例对照受试者。通过5'-核酸外切酶分析（TaqMan）确定HTRA1 -625G>A多态性的基因型。通过聚合酶链反应产物的等位基因特异性消化来确定CFH Y402H基因型。
与对照受试者相比，AMD患者中HTRA1 -625AA基因型携带者的比例显著更高（27.7%对5.1%；p<0.001）。二元逻辑回归分析显示，在根据CFH Y402H基因型进行校正后，与野生型基因型受试者相比，HTRA1 -625A等位基因杂合的受试者患AMD的比值比（OR）为2.7（95%置信区间（CI）：1.1 - 6.8）（p = 0.034）。HTRA1 -625A等位基因纯合的受试者中，OR增加至10.2（95% CI：3.0 - 34.5）（p<0.001）。在根据HTRA1 -625G>A基因型进行校正后，与野生型基因型受试者相比，CFH 402H变异杂合携带者患AMD的OR为3.6（95% CI：1.6 - 7.8）（p = 0.001）。CFH 402HH基因型纯合的受试者中，OR增加至9.8（95% CI：3.7 - 25.9）（p<0.001）。CFH和HTRA1基因型之间的交互项与AMD无显著相关性。
我们的数据表明，在中欧人群中，HTRA1 -625A等位基因和CFH 402H等位基因均与渗出性AMD独立相关。
