Effect of MDR1 gene polymorphism on progression of end-stage renal disease.
OBJECTIVE
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Zhang
Wei-xia
WX
Institute of Clinical Pharmacology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China. weimincai@263.net.
Chen
Bing
B
Zhang
Wen
W
Chen
Nan
N
Yu
Zi-cheng
ZC
Cai
Wei-min
WM
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000483:Alleles; D002681:China / Q000453:epidemiology; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007676:Kidney Failure, Chronic / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D018570:Risk Assessment
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004247:DNA