Specific OCT1 and ABCG2 polymorphisms are associated with Lamotrigine concentrations in Chinese patients with epilepsy.
The pharmacokinetics of Lamotrigine (LTG) varies widely among patients with epilepsy. In this study, we are aiming to investigate the effects of OCT1, ABCG2, ABCC2 and HNF4α genetic polymorphisms on plasma LTG concentrations and therapeutic efficacy in Chinese patients with epilepsy.



The study cohort comprised 112 Han Chinese patients with epilepsy who were receiving LTG monotherapy. Blood samples were taken and LTG levels were measured. The polymorphisms of OCT1 rs2282143, rs628031, ABCG2 rs2231142, rs2231137, ABCC2 rs2273697 and HNF4α rs2071197, rs3212183 were determined. The therapeutic efficacy of LTG at the 1-year time-point was assessed. Data analysis was performed using IBM SPSS Statistics 22.0.



There were significant associations between OCT1 rs628031, ABCG2 rs2231142 polymorphisms and normalized LTG concentrations in patients with epilepsy (P<0.05). On the other hand, polymorphisms of OCT1 rs2282143, ABCG2 rs2231137, ABCC2 rs2273697 and HNF4α rs2071197, rs3212183 exhibited no correlation with LTG concentrations. Additionally, no significant association existed between all the studied genotypes and LTG treatment response.



These results suggested that the polymorphisms of OCT1 rs628031 and ABCG2 rs2231142 may affect LTG metabolism in Chinese patients with epilepsy. However, future studies are necessary to be investigated in a larger cohort of epileptic patients.
Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
Chun-Hong
CH
Shen
Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
Yin-Xi
YX
Zhang
Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
Ru-Yi
RY
Lu
Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
Bo
B
Jin
Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
Shan
S
Wang
Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
Zhi-Rong
ZR
Liu
Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
Ye-Lei
YL
Tang
Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China. Electronic address: meipingd@163.com.
Mei-Ping
MP
Ding
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000235:genetics*; D000328:Adult; D000927:Anticonvulsants / Q000097:blood / Q000627:therapeutic use*; D044466:Asian People / Q000235:genetics; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics*; D050811:Octamer Transcription Factor-1 / Q000235:genetics*; D011110:Polymorphism, Genetic; D016896:Treatment Outcome; D014227:Triazines / Q000097:blood / Q000627:therapeutic use*
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D000927:Anticonvulsants; D051557:Hepatocyte Nuclear Factor 4; D000077213:Lamotrigine; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D050811:Octamer Transcription Factor-1; D014227:Triazines; C000715087:ABCC2 protein, human; C116614:ABCG2 protein, human; C496592:HNF4A protein, human; C494165:POU2F1 protein, human
ABCC2; ABCG2; HNF4α; Lamotrigine; OCT1; Pharmacogenetics