肾透明细胞癌中分泌型卷曲相关蛋白1基因甲基化及其表达与亚甲基四氢叶酸还原酶C677T基因多态性的关系

【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。

The relationship between MTHFR C677T gene polymorphisms,methylation status and expression of SFRP 1 gene in renal clear cell carcinoma

Abstract  Objective  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 controls matched on sex and age was conducted. MTHFR gene C677T polymorphisms were detected by PCR 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.