Goverdhan S V, Hannan S, Newsom R B, Luff A J, Griffiths H, Lotery A J
Clinical Neurosciences Division, University of Southampton, Southampton General Hospital, Southampton, UK.
Eye (Lond). 2008 Jun;22(6):849-54. doi: 10.1038/sj.eye.6702830. Epub 2007 Apr 27.
Mutation in the complement factor H (CFH) gene is an important risk factor for age-related macular degeneration (AMD). In this study, we identified the strength of the CFH Y402H gene variant association in a UK AMD cohort and tested the hypothesis that this variant may influence the biological response of choroidal neovascularisation (CNV) following photodynamic therapy (PDT) for CNV.
A total of 557 cases with AMD and 551 normal controls were genotyped for the CFH Y402H (1277 C/T) variant using the 5' nuclease TaqMan assay for allelic discrimination. The CFH gene association for AMD, for the different CNV subtypes and for patients needing PDT was estimated. Twenty-seven PDT-treated patients were followed up for 15 months with ETDRS-derived vision, clinical examination, and fundus angiography. Individuals with different CFH genotypes were then analysed for any association with visual change following PDT.
The risk association for AMD with the CFH CC genotype (odd ratio (OR)=3.62, Pc<0.0001) was similar to that reported in other Caucasian cohorts. The magnitude and strength of this association was stronger in AREDS stages 2-4 (ORs=4.48, 2.69, and 5.17). ORs for the risk of predominantly classic CNV were significantly raised for both the CC (OR=17.87, P<0.0001) and CT (OR=9.06, P=0.0002) genotypes. The number of patients carrying the high-risk C allele was 70.4% in those requiring PDT as compared to 52.3% in the non-PDT group (OR=2.16, P=0.011), and presence of the CC genotype significantly increased the risk of PDT (OR=5.48, P=0.015). The degree of visual loss following PDT was significantly higher in the CFH CC genotype group (P=0.038); 50% of CC cases (n=13) and 45% of the CT cases (n=12) lost 15 or more ETDRS letters at final follow-up.
In this UK cohort of AMD patients, the CFH Y402H variant was significantly enriched in patients with predominantly classic CNV. Patients homozygous for the CFH Y402H genotype seem to have worse visual acuity after PDT.
补体因子H（CFH）基因突变是年龄相关性黄斑变性（AMD）的重要危险因素。在本研究中，我们确定了英国AMD队列中CFH Y402H基因变异的关联强度，并检验了该变异可能影响脉络膜新生血管（CNV）光动力疗法（PDT）后生物学反应的假设。
使用5'核酸酶TaqMan分析法对557例AMD患者和551例正常对照进行CFH Y402H（1277 C/T）变异的基因分型，以进行等位基因鉴别。估计了CFH基因与AMD、不同CNV亚型以及需要PDT的患者之间的关联。27例接受PDT治疗的患者随访15个月，记录ETDRS视力、临床检查和眼底血管造影结果。然后分析不同CFH基因型个体与PDT后视力变化的相关性。
AMD与CFH CC基因型的风险关联（比值比（OR）=3.62，Pc<0.0001）与其他白种人队列报道的相似。在年龄相关性眼病研究（AREDS）2-4期，这种关联的程度和强度更强（OR分别为4.48、2.69和5.17）。CC基因型（OR=17.87，P<0.0001）和CT基因型（OR=9.06，P=0.0002）的主要典型CNV风险OR值显著升高。需要PDT的患者中携带高危C等位基因的比例为70.4%，而非PDT组为52.3%（OR=2.16，P=0.011），CC基因型的存在显著增加了PDT风险（OR=5.48，P=0.015）。CFH CC基因型组PDT后的视力丧失程度显著更高（P=0.038）；在最终随访时，50%的CC病例（n=13）和45%的CT病例（n=12）视力下降15个或更多ETDRS字母。
在这个英国AMD患者队列中，CFH Y402H变异在主要为典型CNV的患者中显著富集。CFH Y402H基因型纯合子患者在PDT后视力似乎更差。
