ASSOCIATION STUDY OF COMPLEMENT FACTOR H, C2, CFB, AND C3 AND AGE-RELATED MACULAR DEGENERATION IN A HAN CHINESE POPULATION
ASSOCIATION STUDY OF COMPLEMENT FACTOR H, C2, CFB, AND C3 AND AGE-RELATED MACULAR DEGENERATION IN A HAN CHINESE POPULATION
复制标题
补体因子H、C2、CFB、C3与中国汉族年龄相关性黄斑变性的关联研究
DOI：
10.1097/iae.0b013e3181cea676
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发表时间：
2010-09-01
影响因子：
3.3
通讯作者：
Yang, Zhenglin
中科院分区：
文献类型：
--
作者：
Liu, Xiaoqi;Zhao, Peiquan;Yang, Zhenglin
目的：补体途径中的基因，包括补体因子H（CFH）、C2/BF和C3，已被报道与年龄相关性黄斑变性（AMD）相关。在中国大陆汉族人群中，对这些基因的遗传变异，单核苷酸多态性（SNPs）进行基因分型，以进行病例对照关联研究。研究方法：在中国大陆汉族人群中招募了158例湿性AMD患者、80例玻璃膜疣患者和220例匹配的对照受试者。使用ABI SNaPshot方法对CFH中的7个SNP和C2、CFB '和C3中的2个SNP进行基因分型。通过直接聚合酶链反应和凝胶电泳检测到覆盖CFHR 1和CFHR 3基因的84，682个碱基对的缺失。结果如下：CFH中的4个SNPs，包括rs3753394（P = 0.0276）、rs 800292（P = 0.0266）、rs 1061170（P = 0.00514）和rs 1329428（P = 0.0089），在本研究的队列中显示与湿性AMD显著相关。包含这四个SNP的单倍型（CATA）显著增加了对湿性AMD的保护，P值为0.0005，比值比为0.29（95%置信区间：0.15-0.60）。与其他人群不同，rs 2274700和rs 1410996在本研究的中国人群中未显示与AMD显著相关。CFH中的SNP均未显示与玻璃疣显著相关，并且CFH、C2、CFB和C3中的SNP均未显示与本研究队列中的湿性AMD或玻璃疣显著相关。CFHR 1和CFHR 3缺失在中国人群中没有多态性，与湿性AMD或玻璃疣无关。结论：这项研究表明，SNPs rs3753394（P = 0.0276），rs800292（P = 0.0266），rs1061170（P = 0.00514）和rs 1329428（P = 0.0089），但在中国大陆汉族人群中CFH中的rs7535263、rs 1410996或rs 2274700与湿性AMD无显著相关性。本研究发现，CFHR 1和CFHR 3缺失在本研究队列中不存在多态性，并且在白色人群中，C2、CFB和C3基因中与AMD显著相关的SNP均未显示与AMD显著相关，因此，CFH更可能是位于Chr.1q31的AMD易感基因。
Purpose: Genes in the complement pathway, including complement factor H (CFH), C2/BF, and C3, have been reported to be associated with age-related macular degeneration (AMD). Genetic variants, single-nucleotide polymorphisms (SNPs), in these genes were geno-typed for a case-control association study in a mainland Han Chinese population. Methods: One hundred and fifty-eight patients with wet AMD, 80 patients with soft drusen, and 220 matched control subjects were recruited among Han Chinese in mainland China. Seven SNPs in CFH and two SNPs in C2, CFB', and C3 were genotyped using the ABI SNaPshot method. A deletion of 84,682 base pairs covering the CFHR1 and CFHR3 genes was detected by direct polymerase chain reaction and gel electrophoresis. Results: Four SNPs, including rs3753394 (P = 0.0276), rs800292 (P = 0.0266), rs1061170 (P = 0.00514), and rs1329428 (P = 0.0089), in CFH showed a significant association with wet AMD in the cohort of this study. A haplotype containing these four SNPs (CATA) significantly increased protection of wet AMD with a P value of 0.0005 and an odds ratio of 0.29 (95% confidence interval: 0.15-0.60). Unlike in other populations, rs2274700 and rs1410996 did not show a significant association with AMD in the Chinese population of this study. None of the SNPs in CFH showed a significant association with drusen, and none of the SNPs in CFH, C2, CFB, and C3 showed a significant association with either wet AMD or drusen in the cohort of this study. The CFHR1 and CFHR3 deletion was not polymorphic in the Chinese population and was not associated with wet AMD or drusen. Conclusion: This study showed that SNPs rs3753394 (P = 0.0276), rs800292 (P = 0.0266), rs1061170 (P = 0.00514), and rs1329428 (P = 0.0089), but not rs7535263, rs1410996, or rs2274700, in CFH were significantly associated with wet AMD in a mainland Han Chinese population. This study showed that CFH was more likely to be AMD susceptibility gene at Chr.1q31 based on the finding that the CFHR1 and CFHR3 deletion was not polymorphic in the cohort of this study, and none of the SNPs that were significantly associated with AMD in a white population in C2, CFB, and C3 genes showed a significant association with AMD.