[Effect of UGT1A6 genetic polymorphisms on the metabolism of sodium valproate].
OBJECTIVE
To investigate the effect of UGT1A6 genetic polymorphisms on the serum concentration of sodium valproate so as to help better individualize the medication for patients with epilepsy.


METHODS
Peripheral blood samples were collected for 67 patients receiving sodium valproate after more than 5 half-time periods, aged 17.5 (5 - 52). The genotypes of UGT1A6 were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay to examine the alleles 552A-->C. Fluorescence polarization immunoassay (FPIA) was used to measure the serum concentration of sodium valproate and the results were standardized by dosage and body weight.


RESULTS
Out of the 67 cases, 40 (59.7%) were with the wild genotype of UGT1A6 gene, 24 (35.8%) were with the A/C genotype, and 3 (4.5%) were with the C/C genotypes. The frequencies of 552A-->C were 22.4%. The mean value of the serum concentration of sodium valproate with A/A genotype was 4.32 +/- 0.2, significantly higher than that of the patients with A/C genotype (3.43 +/- 0.30, P < 0.05). When the genotypes A/C and C/C were considered as a group, the mean value of the serum concentration of sodium valproate was 3.40 +/- 0.28, significantly lower than that of the patients with A/A genotype (P < 0.05).


CONCLUSIONS
Sodium valproate is metabolized via uridine diphospho-glucuronosyltransferase. The genetic polymorphisms of UGT1A6 gene affect the metabolism of sodium valproate. The dosage of sodium valproate for the patients with 552C allele in UGT1A6 should be more than the usual dosage.
Sun
Yan-ping
YP
Department of Neurology, Affiliated Hospital of Medical College, Qingdao University, Qingdao 266003, China.
Tan
Lan
L
Wang
Yan
Y
Song
Jing-hui
JH
D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000097:blood / Q000235:genetics; D005787:Gene Frequency; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D014635:Valproic Acid / Q000097:blood / Q000378:metabolism*; D055815:Young Adult
D014635:Valproic Acid; C110655:UDP-glucuronosyltransferase, UGT1A6; D014453:Glucuronosyltransferase