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Genetic polymorphisms of human organic anion transporters OATP-C (SLC21A6) and OATP-B (SLC21A9): allele frequencies in the Japanese population and functional analysis.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Nozawa, Takashi Nakajima, Miki Tamai, Ikumi Noda, Kumiko Nezu, Jun-Ichi Sai, Yoshimichi Tsuji, Akira Yokoi, Tsuyoshi |
| Copyright Year | 2002 |
| Abstract | Genetic polymorphisms of human organic anion transporting polypeptides OATP-C (SLC21A6) and OATP-B (SLC21A9) in the Japanese population were analyzed. The allele frequencies of OATP-C*1a, OATP-C*1b (N130D), OATP-C*1c (R152K and D241N), and OATP-C*5 (V174A) were 35.2, 53.7, 0, and 0.7%, respectively, in 267 healthy Japanese subjects. In the OATP-C gene, we found a novel allele called OATP-C*15 possessing two single nucleotide polymorphisms (SNPs), N130D and V174A, simultaneously. The allele frequency of OATP-C*15 was 3.0%. The allele frequencies of OATP-B*1, OATP-B*2 (T392I), and OATP-B*3 (S486F) were 69.1, 0, and 30.9%, respectively. For functional analysis, each OATP-C and OATP-B allele was expressed in human embryonic kidney (HEK293) cells, and the kinetics of uptake of [(3)H]estrone-3-sulfate was determined. In the case of OATP-C alleles, no significant alteration in K(m) or V(max) values of [(3)H]estrone-3-sulfate uptake was observed, even when the V(max) values were corrected for the expression levels of OATP-C protein. In contrast, V(max), corrected with the expression level of OATP-B*3, was decreased to 42.5% of OATP-B*1, whereas the K(m) values were comparable. Since the frequency of the OATP-B*3 allele was high (30.9%) in our subjects, the SNP of S486F may affect the physiological function and/or pharmacological effects of OATP-B substrates in vivo. |
| Starting Page | 9757 |
| Ending Page | 9763 |
| Page Count | 7 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://jpet.aspetjournals.org/content/jpet/302/2/804.full.pdf |
| PubMed reference number | 12130747v1 |
| Volume Number | 302 |
| Issue Number | 2 |
| Journal | The Journal of pharmacology and experimental therapeutics |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Alleles Anions Gene Frequency Genetic Polymorphism Hereditary Diseases Membrane Transport Proteins Nitroprusside Nucleotides Organic Anion Transport Polypeptides Organic Anion Transporters Pharmacology Renal Tissue SLCO1A2 gene SLCO1B1 wt Allele SLCO2B1 wt Allele Single Nucleotide Polymorphism Solute Carrier Organic Anion Transporter Family Member 1b1 |
| Content Type | Text |
| Resource Type | Article |
