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Like other members in CYP2 family, <jats:italic>CYP2C9<\/jats:italic> gene exhibits great genetic polymorphism among different races and individuals. <jats:italic>CYP2C9*18<\/jats:italic> is one <jats:italic>CYP2C9<\/jats:italic> allelic variant identified in a Southeast Asian population and is estimated to cause the amino acid substitutions of I359L and D397A in CYP2C9 enzyme simultaneously. Limited by the low expression level in bacteria and COS\u20107 cells, no valuable enzyme kinetics have been reported on this CYP2C9 variant. In this study, the baculovirus\u2010based system was used for the high expression of recombinant CYP2C9 s in insect cells. As a result, together with I359L substitution, D397A could significantly decrease the protein expression of CYP2C9.18 in insect cells, although substitution of D397A alone had no effect on the expression of CYP2C9 in vitro. As compared with that of wild\u2010type enzyme, both CYP2C9.18 variant and D397A variant could decrease more than 80% of the catalytic activity of CYP2C9 enzyme toward three probe substrates, suggesting that caution should be exercised when patients carrying <jats:italic>CYP2C9*18<\/jats:italic> taking medicines metabolized by CYP2C9 enzyme with a narrow therapeutic window.<\/jats:p>","DOI":"10.1002\/prp2.718","type":"journal-article","created":{"date-parts":[[2021,1,29]],"date-time":"2021-01-29T01:22:04Z","timestamp":1611883324000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Functional characterization of the defective CYP2C9 variant <i>CYP2C9*18<\/i>"],"prefix":"10.1002","volume":"9","author":[{"given":"Jian","family":"Liu","sequence":"first","affiliation":[{"name":"The Key laboratory of Geriatrics Beijing Institute of Geriatrics Beijing Hospital National Center of Gerontology National Health Commission Institute of Geriatric Medicine Chinese Academy of Medical Sciences Beijing P. 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