Functional analysis of a mutation in theSLCO1B1gene (c.1628T>G) identified in a Japanese patient with pravastatin-induced myopathy

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In the present study, we analyzed the function of a novel mutation (c.1628T>4G, p.Leu543Trp) in the solute carrier organic anion transporter (SLCO) 1B1 gene, encoding organic anion transporting polypeptide (OATP) 1B1, which was identified in a patient with pravastatin-induced myopathy. OATP1B1 variants carrying the mutation (OATP1B1*1a+c.1628T>G or *1b+c.1628T>G) showed a reduced transporting activity toward typical substrates and pravastatin compared with the activity of the references (OATP1B1*1a or *1b). This was due to reduction in Vmax values of the variants, not due to change in their Km values. OATP1B1*1b+c.1628T>G was normally expressed on the plasma membrane of HEK293 cells at the same level as that of OATP1B1*1b. Taken together, our results suggest that the mutation c.1628T>G (p.Leu543Trp) reduced the function of OATP1B1 probably due to decrease in turnover rate of one OATP1B1 molecule rather than impairment of protein sorting to the plasma membrane.

The Pharmacogenomics Journal (2009) 9, 185-193; doi:10.1038/tpj.2009.3; published online 24 February 2009

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