南方医科大学学报

南方医科大学学报 ›› 2018, Vol. 38 ›› Issue (08): 986-.

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TGF-β基因启动子-509C/T位点多态性与桂西壮族IgA肾病核心家系的关联性及其铁皮石斛的治疗效果

李仕良，王洁，黄鹏，古贤君，黄美英，黄非凡   

  • 出版日期:2018-08-20 发布日期:2018-08-20

Correlation between TGF-β gene promoter-509C/T polymorphism and IgA nephropathy in core families in Guangxi Zhuang Autonomous Region and the therapeutic effect of dendrobium

  • Online:2018-08-20 Published:2018-08-20

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摘要： 目的探讨IgA肾病（IgAN）患者转化生长因子-β（TGF-β）的启动子-509C/T位点多态性及铁皮石斛处方的疗效。方法采 用PCR-RFLP和直接测序法鉴定118例桂西壮族IgA肾病患者，按TGF-β1基因测序情况，分为CC、CT和TT三种类型，每种类 型随机分为试验组和观察组。另外选取入选患者的兄弟姐妹118例作为家系对照组，采用传递不平衡检验和HRR分析的方法 观察TGFβ1-509 C/T在患病子代的不平衡传递。随机抽取具有至少1名健康的兄弟姐妹同胞的壮族IgA N患者，检测患者和核 心家系成员的TGF-β基因型，在激素联合ACEI/ARB基础上观察铁皮石斛处方的干预效果，并检测患者尿蛋白定量（24 hUpr）、 血清白蛋白（ALB）、肌酐（Scr）、尿素氮（BUN）水平的变化情况。结果桂西壮族IgA N患者TGF-β1 启动子-509C/T位点基因 CC 型32例（占27.1%），CT 型58例（占49.2%），TT型28例（占23.7%）。而IgAN患者核心家系人群为CC 型33例（占28.4%）， CT 型55例（占46.6%），TT型30例（占25.0%）。治疗前试验组与观察组差异无统计学意义（P>0.05），治疗后，CC型：试验组24 hUpr、Scr、BUN水平降低的幅度较观察组高（P<0.01 或P<0.05）。ALB水平升高的幅度较观察组高，但其差异无统计学意义 （P>0.05）；CT型：24 hUpr和BUN水平降低的幅度较观察组高（P<0.01）。Scr水平降低的幅度较观察组高，ALB水平降低的幅 度较观察组高，但其差异无统计学意义（P>0.05）；TT型：24 hUpr、BUN水平降低的幅度较观察组高（P<0.01或P<0.05）。ALB 水平升高的幅度较观察组高（P<0.01）。Scr水平降低的幅度较观察组高，但差异无统计学意义（P>0.05）。结论桂西壮族居民 TGF-β启动子-509C/T 位点多态性与IgA N患病无关联性；西药联合铁皮石斛处方治疗可有效提高IgA N的临床疗效；携带 TGF-β启动子-509基因位点CC型的患者，不仅对西医治疗敏感，对铁皮石斛处方联合干预效果更敏感。

Abstract: Objective To investigate the correlation between transformation growth factor (TGF- β) polymorphisms and IgA nephropathy and the therapeutic effect of dendrobium on IgA nephropathy. Methods Polymerase chain reaction- restriction fragment length polymorphism (PCR- RFLP) and direct sequencing were used for analysis of 118 patients with IgA nephropathy from core families in Guangxi Zhuang Autonomous Region. The imbalanced transfer of TGF iso1-509 C/T in the affected offsprings was observed by transfer imbalance test and HRR analysis. The TGF-β genotype of the patients and the core family members were detected. The therapeutic effects of Dendrobium candidum combined with hormone and ACEI/ ARB treatments were evaluated by observing the patient’s urine protein (24 hUpr), serum albumin (ALB), creatinine (Scr) and urea nitrogen (BUN) levels. Results In the 118 patients with IgA nephropathy, we identified TGF-β 1 promoter -509C/T genotype CC in 32 (27.1%) cases, CT in 58 (49.2%) cases, and TT in 28 (23.7%) cases. In the core family of the patients, CC genotype was found in 33 (28.0%) cases, CT in 55 (46.6%) cases, and TT in 30 (28.0%) cases. The treatments significantly lowered 24 hUpr, Scr, and BUN levels (P>0.05) in patients with CC genotype, significantly lowered 24 hUpr and BUN levels in patients with CT genotype (P<0.05), and significantly lowered 24 hUpr and BUN level and increased (P<0.05) ALB level (P< 0.01) in patients with TT genotype. Conclusion There is no significant correlation between TGF-β promoter - 509C/T polymorphism and IgA nephropathy. The patients with CC genotype are sensitive to the treatments with hormone and ACEI/ ARB and show a stronger response to combined treatments with dendrobium.