Effects of UGT1A4 genetic polymorphisms on serum lamotrigine concentrations in Chinese children with epilepsy.
Lamotrigine (LTG) is widely used in the treatment of children with epilepsy. Genetic polymorphisms in genes encoding drug-metabolizing enzymes may be an important source of interindividual variability in LTG metabolism. The aim of this study was to evaluate the effects of genetic polymorphisms of uridine diphosphate glucuronosyltransferase (UGT) 1A4 (UGT1A4) gene on LTG serum concentrations in children with epilepsy. The UGT1A4 142T > G in the coding regions and -219C > T/-163G > A in the 5'-upstream regions were genotyped using polymerase chain reaction amplification followed by direct automated DNA sequencing in 148 patients treated with polytherapy with LTG and valproic acid (VPA). Our data showed that patients carrying the variant UGT1A4 -219C > T/-163G > A genotypes or alleles had significantly higher adjusted LTG concentrations than those carrying the wild-type genotypes or alleles. However, the significant association was abrogated after adjusted by age, body weight, and adjusted VPA concentration. No associations were detected between the UGT1A4 142T > G genotypes or alleles and adjusted LTG concentrations. Taken together, these results suggest that the -219C > T/-163G > A mutations in the 5'-upstream regions of the UGT1A4 gene affect LTG pharmacokinetics, with which is potentially interfered by age, body weight, and concomitant VPA administration.
Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang, 110004, China.
Qiuning
Q
Wang
School of Life Sciences, Jilin University, Changchun, 130021, China.
Min
M
Liang
School of Life Sciences, Jilin University, Changchun, 130021, China.
Yang
Y
Dong
School of Life Sciences, Jilin University, Changchun, 130021, China.
Wenting
W
Yun
Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang, 110004, China.
Feng
F
Qiu
Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang, 110004, China. Electronic address: zhaolm@sj-hospital.org.
Limei
L
Zhao
School of Life Sciences, Jilin University, Changchun, 130021, China. Electronic address: guoyingjie@jlu.edu.cn.
Yingjie
Y
Guo
D000293:Adolescent; D000927:Anticonvulsants / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D002681:China; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology; D005260:Female; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006801:Humans; D007223:Infant; D000077213:Lamotrigine; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D014227:Triazines / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D014635:Valproic Acid / Q000008:administration & dosage / Q000627:therapeutic use
D000927:Anticonvulsants; D014227:Triazines; C019787:bilirubin glucuronoside glucuronosyltransferase; D014635:Valproic Acid; D014453:Glucuronosyltransferase; D000077213:Lamotrigine
Epilepsy; Genetic polymorphism; Lamotrigine; Serum concentration; UGT1A4