Center for Human Molecular Biology and Genetics, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Sichuan, China.
Retina. 2010 Sep;30(8):1177-84. doi: 10.1097/IAE.0b013e3181cea676.
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.
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）有关。本研究在中国大陆汉族人群中进行了一项病例对照关联研究，对这些基因中的遗传变异（单核苷酸多态性[SNP]）进行了基因分型。
方法：在中国大陆汉族人群中，招募了 158 名湿性 AMD 患者、80 名软性玻璃膜疣患者和 220 名匹配对照。采用 ABI SNaPshot 方法对 CFH 中的 7 个 SNP 和 C2、CFB'、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覆盖 CFHR1 和 CFHR3 基因的 84682 个碱基对的缺失。
结果：在本研究队列中，CFH 中的 4 个 SNP（rs3753394，P = 0.0276；rs800292，P = 0.0266；rs1061170，P = 0.00514；rs1329428，P = 0.0089）与湿性 AMD 显著相关。包含这 4 个 SNP 的单倍型（CATA）显著增加了湿性 AMD 的保护作用，P 值为 0.0005，优势比为 0.29（95%置信区间：0.15-0.60）。与其他人群不同，rs2274700 和 rs1410996 在本研究的中国人群中与 AMD 无显著相关性。CFH 中的任何 SNP 均与玻璃膜疣无显著相关性，CFH、C2、CFB 和 C3 中的任何 SNP 与本研究队列中的湿性 AMD 或玻璃膜疣均无显著相关性。CFHR1 和 CFHR3 缺失在中国人中不是多态性的，与湿性 AMD 或玻璃膜疣无关。
结论：本研究表明，CFH 中的 SNPs rs3753394（P = 0.0276）、rs800292（P = 0.0266）、rs1061170（P = 0.00514）和 rs1329428（P = 0.0089），但不是 rs7535263、rs1410996 或 rs2274700，与中国大陆汉族人群的湿性 AMD 显著相关。本研究发现，基于 CFHR1 和 CFHR3 缺失在本研究队列中不是多态性的，以及在白人人群中与 AMD 显著相关的 C2、CFB 和 C3 基因中的任何 SNP 与 AMD 均无显著相关性，CFH 更有可能成为 1q31 上的 AMD 易感基因。
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