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Published on: May 10, 2024
[Effect of UGT1A6 genetic polymorphisms on the metabolism of sodium valproate]
Yan-ping Sun1, Lan Tan, Yan Wang
1Department of Neurology, Affiliated Hospital of Medical College, Qingdao University, Qingdao 266003, China.
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.
Result:
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.
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