Hepatocyte nuclear factor 1 alpha is a factor responsible for the interindividual variation of OATP1B1 mRNA levels in adult Japanese livers.
OBJECTIVE
The aim of the present study was to clarify the factors responsible for interindividual variability of organic anion transporting polypeptide (OATP, gene symbol SLCO) 1B1 mRNA expression level in the human liver.


METHODS
OATP1B1 mRNA expression levels were determined by real-time PCR in 31 human liver samples. The results were analyzed in relation to a single nucleotide polymorphism (-11187G>A) located in the promoter region and levels of hepatocyte nuclear factor (HNF) 1alpha mRNA.


RESULTS
There was a 4.9-fold interindividual variability of OATP1B1 mRNA expression level in the livers analyzed, which was not associated with -11187G>A polymorphism. Accordingly, the -11187G>A polymorphism did not alter the SLCO1B1 gene promoter activity in luciferase assays. On the other hand, OATP1B1 mRNA levels showed a significant correlation with HNF1alpha mRNA levels (r=0.83, P<0.0001). This correlation was consistent with the results of luciferase assays and chromatin immunoprecipitation assays showing functional interaction between HNF1alpha and SLCO1B1 gene promoter.


CONCLUSIONS
Our results suggest that HNF1alpha is an essential regulator of OATP1B1 mRNA expression and thus the level of HNF1alpha expression is one of the major determinants of interindividual variability in OATP1B1 mRNA expression.
Furihata
Tomomi
T
Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8675, Japan. tomomif@p.chiba-u.ac.jp
Satoh
Tomomi
T
Yamamoto
Naoko
N
Kobayashi
Kaoru
K
Chiba
Kan
K
D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D017930:Genes, Reporter; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007564:Japan; D008099:Liver / Q000378:metabolism*; D027381:Liver-Specific Organic Anion Transporter 1; D008156:Luciferases / Q000235:genetics; D008297:Male; D008875:Middle Aged; D027361:Organic Anion Transporters / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
C496487:HNF1A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; D012333:RNA, Messenger; C503999:SLCO1B1 protein, human; D008156:Luciferases