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Polymorphisms in cytochrome P450 oxidoreductase and its effect on drug metabolism and efficacy

Gong, Lianga,b; Zhang, Cong-Mina,b; Lv, Jin-Fenga,b; Zhou, Hong-Haoa,b; Fan, Lana,b

doi: 10.1097/FPC.0000000000000297

Cytochrome P450 oxidoreductase (POR) has played a potential role in the metabolism of drugs and steroids by supplying electrons to microsomal cytochrome P450 (CYP) enzymes. More than 200 different POR mutations and polymorphisms causing more than 130 amino acid changes in the POR protein have been reported since 2004. A503V is a common amino acid sequence variant encoded by POR*28, whereas A287P and R457H are the most common disease-causing mutations in Europeans and Asians, respectively. Polymorphisms in the POR gene can affect POR activity, CYP-mediated drug metabolism activities, and the efficacy of several clinically used drugs. The effects of POR variants on CYP activities are substrate dependent. In this review, recent research on the effects of POR genetic polymorphisms on drug metabolism and therapy has been summarized and discussed, which can contribute to the rational use of drugs in clinic and the development of personalized medicine.

aDepartment of Clinical Pharmacology, Xiangya Hospital

bInstitute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, People’s Republic of China

Correspondence to Lan Fan, Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, People’s Republic of China Tel: +86 731 8480 5380; fax: +86 731 8235 4476; e-mail:

Received November 9, 2016

Accepted June 23, 2017

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