Hughes Anne E, Mullan Gemma M, Bradley Declan T
Centre for Public Health, Queen's University Belfast, UK.
Mol Vis. 2011 Apr 20;17:983-8.
The 32Q (rs641153; A) and 32W (rs12614; T) variants of complement factor B (CFB) cause less efficient complement activation in vitro than the common 32R variant. This is thought to be the reason that the 32Q variant is associated with decreased risk of age-related macular degeneration (AMD). We investigated whether the 32W variant was also associated with decreased risk of AMD.
We genotyped 367 cases with neovascular AMD and 251 disease-free controls. Association with the disease phenotype was assessed by logistic regression for polymorphisms of CFB alone and in combination with smoking status and genetic risk markers of complement factor H (CFH) and HtrA serine peptidase 1 (HTRA1). We performed meta-analysis of all previously published reports of 32W allele frequency in AMD cases and controls.
The CFB variant 32W was associated with protection against neovascular AMD, compared to the common 32R variant (odds ratio 0.64, p<0.05, in logistic regression with CFB variants; odds ratio 0.53, p<0.05, in logistic regression with CFB variants, CFH haplotypes, HTRA1 rs10490924 genotype, and smoking status). Meta-analysis (n=1,795) including this study and two others of neovascular AMD showed a combined odds ratio of 0.75 (p<0.05) for 32W, compared to 32R. Meta-analysis (n=2,600) of all reported studies of all types of AMD showed a combined odds ratio of 0.79 (p<0.01).
Our study shows that the 32W variant of CFB is associated with protection against AMD, in keeping with evidence of its functional effect on the complement system. The protective effect is less strong than that associated with 32Q.
补体因子B（CFB）的32Q（rs641153；A）和32W（rs12614；T）变异体在体外引起的补体激活效率低于常见的32R变异体。这被认为是32Q变异体与年龄相关性黄斑变性（AMD）风险降低相关的原因。我们研究了32W变异体是否也与AMD风险降低相关。
我们对367例新生血管性AMD患者和251例无病对照进行了基因分型。通过逻辑回归分析CFB多态性单独以及与吸烟状态、补体因子H（CFH）和HtrA丝氨酸蛋白酶1（HTRA1）的遗传风险标志物联合时与疾病表型的关联。我们对先前发表的所有关于AMD病例和对照中32W等位基因频率的报告进行了荟萃分析。
与常见的32R变异体相比，CFB变异体32W与预防新生血管性AMD相关（在CFB变异体的逻辑回归中比值比为0.64，p<0.05；在CFB变异体、CFH单倍型、HTRA1 rs10490924基因型和吸烟状态的逻辑回归中比值比为0.53，p<0.05）。包括本研究和另外两项新生血管性AMD研究的荟萃分析（n=1795）显示，与32R相比，32W的合并比值比为0.75（p<0.05）。对所有已报道的各类AMD研究（n=2600）进行的荟萃分析显示，合并比值比为。
我们的研究表明，CFB的32W变异体与预防AMD相关，这与其对补体系统的功能作用证据一致。其保护作用不如与32Q相关的保护作用强。
