Correlation between UGT1A4-142T>G gene polymorphisms and plasma concentrations of lamotrigine in children with bipolar disorder
Objective To analyze the impact of UGT1A4-142T>G gene polymorphism on the plasma concentration of lamotrigine in children with bipolar disorder.Methods Blood samples were collected from patients with bipolar disorder who were treated with lamotrigine for at least 21 days between January 2019 and May 2024 at the People's Hospital of Xinjiang Uygur Autonomous Region.The plasma concentration of lamotrigine was determined using ultra-high-performance liquid chromatography.The UGT1A4-142T>G genotype of the children was detected using the first-generation Sanger sequencing method,and the correlation between the UGT1A4-142T>G gene polymorphism and the plasma concentration of lamotrigine was analyzed.Results A total of 82 children were enrolled,including 14 males and 68 females,with an average age of(15.51±1.72)years.The average dosage of lamotrigine was(196.54±90.25)mg/d and the average plasma concentration of lamotrigine was(4.66±2.64)μg/mL.The average concentration-to-dose ratio(CDR)was(1.44±1.22)μg·kg/(mL·mg).There was a positive correlation between the plasma concentration of lamotrigine and the dosage(r=0.541,P<0.05).The UGT1A4-142T>G genotypes were distributed as follows:TT genotype(52 cases),GT genotype(25 cases),and GG genotype(5 cases).Comparisons of gender,age,BMI,lamotrigine dosage,plasma concentration of lamotrigine,and CDR among children with different UGT1A4-142T>G genotypes showed statistically significant differences(P<0.05).Specifically,children with the GG genotype were older than those with the TT genotype[(16.34±1.19)years vs(15.77±1.54)years],had lower BMI than the TT genotype[(18.69±2.34)kg/m2 vs(20.72±3.53)kg/m2],and had higher plasma concentration of lamotrigine than the TT genotype[(5.63±1.48)μg/mL vs(4.56±2.82)μg/mL],with all differences being statistically significant(P<0.05).Children with the GT genotype had lower BMI and lamotrigine dosage than the TT genotype[(19.87±5.01)kg/m2 vs(20.72±3.53)kg/m2,(164.79±77.95)mg/d vs(208.26±86.95)mg/d],and higher CDR than the TT genotype[(1.78±1.24)μg·kg/(mL·mg)vs(1.33±1.15)μg·kg/(mL·mg)],with all differences being statistically significant(P<0.05).Conclusion The UGT1A4-142T>G gene mutation affects the plasma concentration of lamotrigine,and it is recommended to test the genetic phenotype of UGT1A4-142T>G before using lamotrigine in children with bipolar disorder.
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