补体因子H基因单核苷酸多态性与渗出型老年性黄斑变性易感性的相关性研究

The correlation between single nucleotide polymorphism of complement factor H gene and exudative age-related macular degeneration

目的探讨渗出型老年性黄斑变性（AMD）易感性与补体因子H（CFH）基因单核苷酸（SNP）多态性的相关性。方法病例对照研究。136例渗出型AMD患者（AMD组）和年龄、性别与之匹配的140名正常健康者（对照组）纳入研究。取得所有受检者的知情同意后，抽取晨起空腹肘静脉血4ml，提取基因组DNA。采用多聚酶链反应和特异性限制内切酶消化法检测CFHY402H（rsl061170）、CFH-257C〉T（rs3753394）及cFHIVSl5（rsl329428）的基因型和等位基因。采用SHEsis软件构建单倍型，对比分析两组CFH基因SNP不同单倍型的频率。分析cFH基因SNP不同等位基因、基因型和单倍型与渗出型AMD的相关性。结果CFHY402H（rs1061170）存在TT、TC、CC3种基因型，等位基因位于位点T、C；CFH257C〉T（rs3753394）存在CC、CT、TT3种基因型，等位基因位于位点C、T；CFH IVS15（rs1329428）存在AA、AG、GG3种基因型，等位基因位于位点A、G。AMD组、对照组CFH基因型和等位基因频率比较，差异均有统计学意义（P〈0．05）。CFHY402H（rs1061170）的杂合子基因型TC、CFH-257C〉T（rs3753394）的纯合子基因型TT及CFHIVSl5（rsl329428）的纯合子基因型GG均与渗出型AMD有相关性（OR=4．11，2．55，3．1l；P〈0．05）；等位基因T、C、G为风险等位基因（OR=3．14，1．72，1．79；P〈0．05）。AMD组和对照组单倍型TCG、CTG及CTA频率间差异有统计学意义（X2=10．53，6．60，32．82；P〈0．05）；其余单倍型频率间差异无统计学意义（P〉0．05）。结论CFH基因SNP多态性与渗出型AMD易感性有关。

Objective To investigate the correlation between single nucleotide polymorphism （SNP） of complement factor H （CFH） gene and exudative age-related macular degeneration （AMD） susceptibility. Methods This is a retrospective case control study. 136 exudative AMD patients （AMD group） and 140 age- and sex-matched normal subjects （control group） were enrolled in this study. The peripheral blood was collected, polymorphism genotypes and frequency of CFH Y402H （rs1061170）, CFH -257C 〉 T （rs3753394） and CFH IVS15 （rs1329428）were measured by polymerase chain reaction （PCR） and allelespecific restriction endonuclease digestion. The SHEsis software was performed on haplotype construction to analyze the frequency. Results There are TT, TC, CC genotypes and T, C allele in CFH Y402H （rs1061170）; CC, CT, TT genotypes and C, T allele in CFH -257C〉T （rs3753394）; AA, AG, GG genotypes and A, G allele in CFH IVS15 （rs1329428）. The differences of genotypes and allele frequency between 2 groups were statistically significant （P〈0.05）. The TC genotype in CFH Y402H, TT genotype in CFH -257C〉T （rs3753394） and GG genotype in CFH IVS15 （rs1329428） were associated with exudative AMD susceptibility （OR=4.11,2.55,3.11;P〈0.05）. The T, C and G allele were the risk alleles （OR= 3.14,1.72,1.79;P〈0.05）. The differences of frequency between TCG, CTG and CTA haplotype were statistically significant（x2 = 10.53,6.60, 32.82;P〈0.05）. Conclusion There is correlation between SNPs of CFH gene and exudative AMD susceptibility.