E-钙粘蛋白基因遗传变异与子宫内膜异位症的关联研究

Study on the associations of E-cadherin gene polymorphisms with the risk of endometriosis

目的：探讨E-钙粘蛋白（E—cadherin，CDH1）基因遗传变异与子宫内膜异位症（EMS）发病风险的关系。方法：采用病例．对照研究方法，DNA测序技术分析㈣基因启动子区、所有外显子和3’非翻译区（3’-UTRlSNPs位点，从中筛选出6个候选位点（rs16260、rs28372783、rs1801552、rs1801026、rs8049282、rs13689）。扩大样本，通过聚合酶链反应-连接酶检测反应（PCR．LDR）方法检测651例EMS患者f病例组）和655名健康对照妇4r（对照组）6个SNPs位点的基因型频率分布情况。结果：DNA测序结果显示蚴基因启动子区、所有外显子和3’-UTR的17个SNP位点中15个位点在NCBI数据库中有记载，而2个位点尚无相关记载，位于3＇-UTR＋759和3’-UTR＋1445。统计学分析显示6个候选的SNPs基因型和等位基因在病例组和对照组间的频率分布均无统计学差异（p〉0．05）。但进一步分层分析显示，rs8049282C／T多态可能与EMS患者的原发不孕相关，即与CT＋TT基因型相比，CC基因型可显著增加EMS患者原发不孕的风险（OR=2．25，95％CI=1．32-3．83）。结论：㈣基因启动子区、外显子和3’-UTR区的遗传变异可能与中国北方汉族妇女EMS的发病风险无关．但rs8049282C／T多态可能是EMS患者原发不孕的潜在危险因素。

Objective： To investigate the associations of single nucleotide polymorphisms （SNPs） of the E-cadherin （CDH1） gene with endometriosis （EMS）. Methods： SNPs in the promoter region, exons, and 3＇-UTR of the CDH1 gene were identified by direct sequencing in women with EMS and control women. Genotyping analysis was performed using polymerase chain reaction and ligase detection reaction （PCR-LDR） in 651 women with EMS and 655 control women for the 6 selected SNPs （rs16260, rs28372783, rs1801552, rs1801026, rs8049282, rs13689）. Results： In total, 17 SNPs were reported by direct sequencing among which 15 SNPs had been recorded in the NCBI database, while there was no record of 2 SNPs located in 3＇-UTR at ＋759 and ＋1445. There were no significant associations between the SNPs and the risk of developing EMS （P〉0.05）. But further stratified analysis found that the CC genotype of rs8049282 may significantly increase the risk of primary infer- tility in patients with ovarian EMS （OR=2.25, 95%CI=1.32-3.83）. Conclusion： SNPs in the promoter region, exons, and 3＇-UTR of the CDH1 gene may be not associated with the risk of developing EMS in northern Chinese women. But the rs8049282 SNP of the CDH1 gene may be a potential risk factor of EMS-related infertility.