Department of Ophthalmology, Peking University People's Hospital, Beijing, China.
Invest Ophthalmol Vis Sci. 2014 Apr 17;55(4):2534-8. doi: 10.1167/iovs.13-13437.
To investigate whether 11 variants in complement factor H gene contributed differently in patients with neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) of Chinese descent.
We performed a case-control study in a group of Chinese patients with nAMD (n = 344) or PCV (n = 368) and contrasted the results against an independent control group comprising 511 mild cataract patients without any evidence of age-related maculopathy. Association analysis of allele and genotype frequencies was performed for 11 haplotype-tagging single-nucleotide polymorphisms (SNPs) at the CFH locus (rs1061170, rs1329428, rs1410996, rs2284664, rs375396, rs529825, rs551397, rs7540032, rs800292, rs2274700, and rs1065489). Multinomial logistic regression analyses were performed to estimate and compare the effect of these 11 CFH polymorphisms on AMD and PCV, using the wild-type genotype as reference. Differences in the observed genotypic distributions between cases and controls were tested by using χ(2) tests, with age and sex adjusted for using logistic regression.
CFH rs1065489 was not significantly associated with the nAMD phenotype in Chinese collections either on univariate or multivariate analysis (P > 0.05 for all comparisons). The other 10 SNPs of CFH were significantly associated with the nAMD phenotype. As for PCV, all 11 SNP markers were significantly associated with risk of PCV before or after correction for age and sex differences. Eight of the 11 SNP markers showed significant evidence of heterogeneity between AMD and PCV (P < 0.05 for all comparisons).
Our data suggest that the genetic architecture at the CFH locus is complex with some markers showing significant skewing of the genotypes toward nAMD or PCV in Asians. This further supports the clinical observation that nAMD and PCV could have distinct pathogenesis mechanisms, which will require larger studies to accurately dissect.
研究 11 种补体因子 H 基因变异在中国裔新生血管性年龄相关性黄斑变性（nAMD）和息肉状脉络膜血管病变（PCV）患者中的作用是否不同。
我们对一组中国 nAMD（n=344）或 PCV（n=368）患者进行了病例对照研究，并将结果与由 511 名无年龄相关性黄斑病变证据的轻度白内障患者组成的独立对照组进行对比。对 CFH 基因座（rs1061170、rs1329428、rs1410996、rs2284664、rs375396、rs529825、rs551397、rs7540032、rs800292、rs2274700 和 rs1065489）的 11 个单体型标签单核苷酸多态性（SNP）进行了等位基因和基因型频率的关联分析。使用多元逻辑回归分析，以野生型基因型为参考，估计并比较这 11 个 CFH 多态性对 AMD 和 PCV 的影响。使用 χ²检验比较病例组和对照组观察到的基因型分布差异，并使用逻辑回归校正年龄和性别。
在单变量或多变量分析中，CFH rs1065489 与中国人群 nAMD 表型均无显著相关性（所有比较的 P>0.05）。CFH 的其他 10 个 SNP 与 nAMD 表型显著相关。对于 PCV，在校正年龄和性别差异之前或之后，11 个 SNP 标记物均与 PCV 风险显著相关。在 AMD 和 PCV 之间，11 个 SNP 标记物中有 8 个显示出显著的异质性证据（所有比较的 P<0.05）。
我们的数据表明，CFH 基因座的遗传结构很复杂，一些标记物在亚洲人群中显示出 nAMD 或 PCV 基因型的显著偏倚。这进一步支持了 nAMD 和 PCV 可能具有不同发病机制的临床观察，这需要更大的研究来准确剖析。
