Functional analysis of a mutation in the SLCO1B1 gene (c.1628T>G) identified in a Japanese patient with pravastatin-induced myopathy.

In the present study, we analyzed the function of a novel mutation (c.1628T>G, 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 V(max) values of the variants, not due to change in their K(m) 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.