Zhang Wei-xia, Chen Bing, Zhang Wen, Chen Nan, Yu Zi-cheng, Cai Wei-min
Institute of Clinical Pharmacology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
Acta Pharmacol Sin. 2007 Apr;28(4):579-83. doi: 10.1111/j.1745-7254.2007.00517.x.
P-glycoprotein is localized at the apical brush-border membrane of the proximal renal tubule and functions as extruding toxins and xenobiotics out of cells. The difference of P-glycoproteinos function resulted from single nucleotide polymorphisms in MDR1 (multidrug resistance gene encoding for P-gp) and may be the cause of interindividual differences in susceptibility to end-stage renal disease (ESRD). The purpose of this study is to compare the genotype frequency of C3435T and G1199A polymorphisms in MDR1 between ESRD patients and healthy controls in the Chinese population to determine whether the alteration of the P-gp function is associated with ESRD.
Two hundred and eighty-four healthy Chinese controls and 244 Chinese patients with ESRD were involved in this study. Allele specific PCR and polymerase chain reaction-restriction fragment length polymorphism assay were used to determine the genotype MDR1 G1199A and C3435T, respectively.
The genotype distribution of 3435CC, 3435CT, and 3435TT were 0.35, 0.50, and 0.15, respectively, in the control group and 0.38, 0.47, and 0.15 in the group with the ESRD patients. No variant allele 1199G>A was found in any of the patients. The value of serum creatinine for genotypes 3435CC, 3435CT, and 3435TT in the ESRD patients were 753.8+/-276.0 mumol/L, 849.6+/-342.2 micromol/L, and 987.0+/-512.0 micromol/L, respectively. The difference between 3435TT and 3435CC reached statistical significance (P<0.05).
The low expression of P-glycoprotein was not the etiological factor for the kidney disease, but it may contribute to the progression of ESRD and affect the severity. Chinese people do not carry the 1199G>A variant allele. More studies are needed to clarify the cause and interindividual differences in the susceptibility for the risk of ESRD.
P - 糖蛋白定位于近端肾小管的顶端刷状缘膜，其功能是将毒素和外源性物质排出细胞。P - 糖蛋白功能的差异源于多药耐药基因1（MDR1，编码P - 糖蛋白）中的单核苷酸多态性，这可能是个体终末期肾病（ESRD）易感性存在差异的原因。本研究旨在比较中国人群中ESRD患者与健康对照者MDR1基因C3435T和G1199A多态性的基因型频率，以确定P - 糖蛋白功能的改变是否与ESRD相关。
本研究纳入了284名健康中国对照者和244名中国ESRD患者。分别采用等位基因特异性PCR和聚合酶链反应 - 限制性片段长度多态性分析来确定MDR1基因G1199A和C3435T的基因型。
对照组中3435CC、3435CT和3435TT的基因型分布分别为0.35、0.50和0.15，ESRD患者组中分别为0.38、0.47和0.15。所有患者均未发现1199G > A变异等位基因。ESRD患者中3435CC、3435CT和3435TT基因型的血清肌酐值分别为753.8±276.0μmol/L、849.6±342.2μmol/L和987.0±512.0μmol/L。3435TT与3435CC之间的差异具有统计学意义（P < 0.05）。
P - 糖蛋白低表达不是肾病的病因，但可能促进ESRD的进展并影响其严重程度。中国人不携带1199G > A变异等位基因。需要更多研究来阐明ESRD风险易感性的原因及个体差异。
