磷酸二酯酶4D基因单核苷酸多态性与COPD相关性研究

目的 探讨磷酸二酯酶4D (PDE4D)基因单核苷酸多态性(SNP)与COPD相关性.方法 选取8个SNP位点SNP1=rs11740402,SNP2=rs17528473,SNP3=rs17780213,SNP4=rs1529843,SNP5=rs11743928,SNP6=rs26956,SNP7=rs35387,SNP8=rs35386,以北京某社区40～80岁人群为研究对象,共入选136例受试者,COPD组71例和对照组65例,均为汉族.设计目标SNP位点上下游引物,PCR扩增目标片段,Sanger测序法检测目标片段碱基,x2检验比较2组在等位基因和基因型分布频率上的差异,非条件Logistic回归评价SNP位点与COPD之间的相关性.结果 8个SNP位点其基因型分布在COPD组和对照组均符合Hardy-Weinberg平衡,在对照组受试者连锁不平衡(Linkage Disequilibrium,LD)分析时发现SNP1、SNP2处于连锁不平衡,形成LDBlock1,SNP6、SNP7和SNP8处于连锁不平衡,形成LD Block2,SNP5基因型均为A/A型,不能与其他SNP位点形成LD Block.单倍体型分析发现在COPD组和对照组中差异无统计学意义(P＞0.05).基于等位基因的关联分析中发现2组病例之间差异无统计学意义(P＞0.05),在基因型的关联分析中发现位点SNP8基因型频率在COPD组和对照组差异有统计学意义(P＜0.05),在进一步非条件Logistic回归分析中发现SNP8在Ressessive遗传模型时与COPD存在相关性,G/G基因型在COPD组和对照组分别为20.3％和6.3％(P＜0.05,OR =4.07,95％ CI为1.26～13.18),提示SNP8的G/G基因型与COPD易感性增加有关.结论 研究结果提示PDE4D基因SNP可能与COPD的发生发展相关,SNP8的G/G基因型可能是COPD易感性的一个预测因子.

Association of single nucleotide polymorphisms in PDE4D gene with COPD in Chinese population

Objective To investigate the association of single nucleotide polymorphisms (SNP) in PDE4D gene with COPD.Methods Seventy-one COPD patients and 65 control patients of a community in Beijing,aged 40-80 years,were enrolled in the study.Eight SNPs in PDE4D gene were selected SNP1 =rs11740402,SNP2 =rs17528473,SNP3 =rs17780213,SNP4 =rs1529843,SNP5 =rs11743928,SNP6 =rs26956,SNP7 =rs35387,SNP8 =rs35386.DNA specimens were all extracted from frozen blood and primers of two ends were designed to amplify their unique targets under a defined set of reaction conditions.Genotyping was done by Sanger sequencing.The difference of genotype and the variation of allele frequencies were analyzed by Chi-square test.Association between SNPs and COPD was examined by unconditioned logistic regression analysis.Results The polymorphisms of the 8 SNPs in COPD and control patients were all on Hardy-Weinberg balance.The Linkage Disequilibrium analysis revealed a genetic disequilibrium at SNP1 and SNP2,which made LD block 1,and the other genetic disequilibrium at SNP6,SNP7 and SNP8,which made LD block 2.The genotype of SNP5 was A/A in all the patients of the two groups.There was no difference in haplotypes and the frequencies of alleles in the 8 SNPs between the two groups.However,significant difference between the two groups was found at SNP8 (P ＜0.05) in the analysis of genotype frequencies.In further unconditional logistic regression analysis,SNP8 showed significant difference in Ressessive model (P ＜ 0.05,OR =4.07,95％ CI =1.26-13.18) and the frequency of genotype G/G was 20.3 ％ and 6.3 ％ in COPD and control group respectively.Conclusions It was suggested that genetic variants of PDE4D gene might be associated with COPD in the Chinese population.