摘要目的 探讨人肾透明细胞癌组织中分泌型卷曲相关蛋白1基因(SFRP-1)的甲基化状态及其mRNA表达与亚甲基四氢叶酸还原酶C677T (MTHFR C677T)基因多态性的关系.方法 采用PCR-RFLP技术分别检测38例手术切除的肾透明细胞癌区和外周正常肾脏组织标本MTHFR基因677(C→T)多态,并分别以Real-time PCR和和甲基化特异性PCR (MSP)技术检测SFRP 1基因的表达和甲基化状态.结果 SFRP 1基因失表达和/或低表达的肾透明细胞癌组织其启动子区处于高甲基化状态,MTHFR 677CC基因型的肾透明细胞癌组织SFRP 1甲基化升高且其表达降低,SFRP 1的甲基化及其表达与MTHFR C677T基因多态性有明显相关性.结论 MTHFR基因多态性通过影响SFRP 1基因的甲基化状态而调控其表达,可能在肾癌的发生、发展中具有重要作用.

abstractsObjective To investigate the relationship between MTHFR C677T gene polymorphisms,the expression and promoter methylation status of tumor-suppressor gene SFRP-1 in renal clear cell carcinoma.Methods A case-control study consisting of 38 renal cancer cases and 38 con trols matched on sex and age was conducted.MTHFR gene C677T polymorphisms were detected byPCR-RFLP technology,Real-time PCR was used to detect the mRNA expression of SFRP-1,then the status of the SFRP-1 promoter methylations in the tumors was detected using a methylation specific PCR (MSP).Results Promoter hypermethylation was frequently detected in renal cancer tissues that expressed lower level or lost expression of SFRP-1 gene in 677CC genotypes patients,SFRP-1 methylation and expression and MTHFR C677T gene polymorphism has obvious correlation.Conclusions MTHFR gene polymorphisms could effect methylation status and regulate its expression of SFRP-1 gene,it probably plays an important role in process of occurrence and development in renal cell carcinoma.