Multiple gene polymorphisms in the complement factor H gene are associated with exudative age-related macular degeneration in chinese
Multiple gene polymorphisms in the complement factor H gene are associated with exudative age-related macular degeneration in chinese
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DOI：
10.1167/iovs.07-1517
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发表时间：
2008-08-01
影响因子：
4.4
通讯作者：
Pang, Chi Pui
中科院分区：
文献类型：
--
作者：
Ng, Tsz Kin;Chen, Li Jia;Pang, Chi Pui
目的.补体因子H（CFH）基因的变异已被证明与年龄相关性黄斑变性（AMD）密切相关。本研究对163例渗出型AMD患者和155例无血缘关系的中国对照者的CFH基因序列进行了研究。所有22 CFH外显子，内含子-外显子边界，和启动子序列进行了筛选，通过聚合酶链反应和DNA测序。58个序列变化，其中42个新的，被确定。等位基因频率>30%的6个SNP与渗出型AMD显著相关。SNP rs3753396是新的;其余的已报告：rs3753394，rs 551397，rs 800292，rs 2274700和rs 1329428。构建了两个单倍型区组。TG单倍型rs 551397和rs 800292是渗出型AMD易感性增加的主要单倍型（P（corr）= 0.0001，OR = 1.91，95%CI = 1.36-2.68）。这些发现支持了先前的证据，即CFH基因是AMD相关基因之一。CFH变异体在中国人群中的分布模式与其他人群不同。个体SNP和单倍型分析显示CFH 5'端的古老等位基因有助于增加渗出性AMD的易感性。
PURPOSE. Variants in the complement factor H (CFH) gene have been shown to be strongly associated with age-related macular degeneration (AMD). In this study, sequence alterations in CFH were investigated in 163 Chinese patients with exudative AMD and 155 unrelated Chinese control subjects.METHODS. All the 22 CFH exons, intron-exon boundaries, and promoter sequences were screened by polymerase chain reaction and DNA sequencing.RESULTS. Fifty-eight sequence changes, 42 of them novel, were identified. Six SNPs with an allele frequency >30% were significantly associated with exudative AMD. SNP rs3753396 was novel; the rest had been reported: rs3753394, rs551397, rs800292, rs2274700, and rs1329428. Two haplotype blocks were constructed. The TG haplotype for rs551397 and rs800292 was the major haplotype that conferred a significantly increased susceptibility to exudative AMD (P(corr) = 0.0001, OR = 1.91, 95% CI = 1.36-2.68).CONCLUSIONS. The findings support prior evidence that the CFH gene is one of the AMD-associated genes. There is a different distribution pattern of CFH variants in the Chinese compared with other populations. Individual SNP and haplotype analyses revealed that the ancient alleles at the 5' end of CFH contribute to an increased susceptibility to exudative AMD.