Association Study Of Gene Polymorphism With Valproic Acid Serum Concentration In Neurosurgery Surgical Patients

Objective: To study the relationship between the diversity of genes and sodium valproate plasma concentration among the patients which used VPA to prevent epilepsy.The genes include UGT1A3?T31C?, UGT1A6?T19G, A541G?, UGT2B7?A268G,G211T?, CYP2C9?C430T, A1075C?, CYP2C19?G681A, G636A?, CYP3A4?1B:A>G,G:G>A?, its study will provide a data reference for clinical precision medical treatment and individualized treatment program..Method: A total of 152 patients of neurological surgery who taking sodium valproate,hepatic and renal function were normal, were collected; And their distribution of genes including UGT1A3?T31C?, UGT1A6?T19G,A541G?, UGT2B7?A268G,G211 T, C₁61T?,CYP2C9?C430T, A1075C?, CYP2C19?G681A, G636A?, CYP3A4?1B:A>G, 1G:G>A?were detected by Sequenom Mass Array system; The patients' plasma concentration of sodium valpraoate were detected by HPLC.After being analyzed the relationship among gender, weight, and dose to eliminate interference factors, the plasma concentration translate into standardized plasma concentration; The basic information of patients collected in HIS were used to analyze the influence of drug combination; Combining the genes of UGT and CYP with standardized plasma concentration to analyze the influence of UGT and CYP genotypes on patients' VPA plasma concentration.Result: The mulation rate of gens among 122 patients who match gene detect condition:UGT1A3?T31C? is 25.85%; UGT1A6?T19G, A541G? are 24.20% and 23.00%;UGT2B7?A268G, G211 T, C₁61T? are 72.95%, 12.70%, 27.05%; CYP2C9?C430T,A1075C? are 34.85% and 2.85%; CYP2C19?G681A, G636A? are 36.50% and 3.30%;CYP3A4?1B:A>G, 1G:G>A? are 33.15% and 25.80%. The VPA plasma concentration of155 patients were detected by HPLC method.After standardizing, 111 patients did not take the drugs interact with VPA, the standardization plasma concentration was4.064�0.757 ?g�kg�m L-1�mg-1; 15 patients took combination with meropenem, the standardization plasma concentration was 0.751�0.213 ?g�kg�m L-1�mg-1; 12 patients took combination with biapenem, the standardization plasma concentration was1.322�0.494 ?g�kg�m L-1�mg-1; 14 patients take combination with carbamazepine, the standardization plasma concentration was 1.542�0.614 ?g�kg�m L-1�mg-1. Among the111 patients did not take the drugs interact with VPA, whose standardization plasma concentration were higher in patients with UGT1A6?T19G?G/G, CYP2C9?C430T?C/T,CYP2C9?C430T?T/T, CYP2C19?G681A?A/A genes than those with UGT1A6?T19G?T/T,UGT1A6?T19G?T/G, CYP2C9?C430T?C/C, CYP2C19?G681A?G/G,CYP2C19?G681A?G/A genes?P<0.05?. There were no statistical significance in differences of standardization plasma concentration among other genes.Conclusion: 1)The distribution frequency of genes among the patients of neurological surgery is obtained and will improve exact reference data for clinical medicine;2) The HPLC method detecting the plasma concentration of VPA is accrute and useful:Taking VPA with meropenem, biapenem, carbamazepine, patients will be decreased VPA plasma concentration and should avoid the combination of medication; 3)Suggest clinic detect patients' gene polymorphism before use of VPA, patients with one or more of UGT1A6?T19G?G/G, CYP2C9?C430T?C/T, CYP2C9?C430T?T/T,CYP2C19?G681A?A/A genes are PM, which should reduce the dosage; Patients with UGT1A6?T19G?T/T, UGT1A6?T19G?T/G, CYP2C9?C430T?C/C, CYP2C19?G681A?G/G, CYP2C19?G681A? G/A genes are EM, which can follow the dosage with instruction; There is no inference in others.