Correlation between MDR1 methylation status in the promoter region and MDR1 genetic polymorphism in 194 healthy Chinese Han subjects.
OBJECTIVE
To investigate the correlation between the methylation status in the MDR1 promoter region and the MDR1 genetic polymorphism.


METHODS
A total of 194 unrelated subjects (105 men and 89 women) with a median age of 26 years were enrolled in this study. DNA was extracted and PCR-RFLP was performed for C1236T, C3435T and G2677T/A polymorphism genotyping. The combined bisulfite restriction analysis (COBRA) method was also performed to determine DNA methylation levels in the MDR1 promoter region. Genotype frequencies for the variants SNPs were assessed for deviation from Hardy-Weinberg equilibrium using the chi2 test. Nonparametric tests including Kruskal-Wallis method and the Mann-Whitney U test were used to compare the DNA methylation levels between different genotypes.


RESULTS
The allelic frequency distribution of the C1236T, C3435T and G2677T/A was found to be in good agreement with previous reports. Our study revealed significant correlation between different genotypes of C3435T and G2677T/A, but there is no significant difference between the different genotypes of C1236T.


CONCLUSIONS
A correlation between MDR1 genetic polymorphisms C3435T and G2677T/A, as well as haplotypes derived from C1236T, G2677T/A and C3435T, with methylation status of MDR1 promoter region was found in this study. Further investigations are needed to explore the molecular mechanism and clinical significance of this correlation.
Jiang
Zhi-Ping
ZP
Laboratory of Clinical Pharmacology, Department of Hematology, Xiang-Ya Hospital, Central-South University, 87, Xiang-Ya Road, Changsha, 410008, China.
Xu
Ping
P
Liu
Rong-Rong
RR
Li
Huan-De
HD
Wang
Guan-Ping
GP
Zhao
Xie-Lan
XL
Chen
Fan-Ping
FP
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D044466:Asian People / Q000235:genetics*; D019175:DNA Methylation; D003627:Data Interpretation, Statistical; D044127:Epigenesis, Genetic; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D055815:Young Adult
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1