UGT polymorphisms and lamotrigine clearance during pregnancy
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UGT polymorphisms and lamotrigine clearance during pregnancy. / Petrenaite, Vaiva; Öhman, Inger; Ekström, Lena; Sæbye, Ditte; Hansen, Thomas Folkmann; Tomson, Torbjörn; Sabers, Anne.
In: Epilepsy Research, Vol. 140, 2018, p. 199-208.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - UGT polymorphisms and lamotrigine clearance during pregnancy
AU - Petrenaite, Vaiva
AU - Öhman, Inger
AU - Ekström, Lena
AU - Sæbye, Ditte
AU - Hansen, Thomas Folkmann
AU - Tomson, Torbjörn
AU - Sabers, Anne
PY - 2018
Y1 - 2018
N2 - Objective: To evaluate the impact of maternal UGT1A4 and UGT2B7 genetic polymorphisms and sex of foetus on gestation-induced changes in lamotrigine (LTG) clearance during pregnancy and post-partum (PP). Methods: Single nucleotide polymorphisms UGT1A4 142T > G, L48V (*3), UGT1A4 70C > A, P24T (*2) and UGT2B7 802C > T, H268Y (*2) were determined in 40 women (47 pregnancies) with epilepsy treated with LTG. Retrospectively collected data included LTG dosage and LTG plasma levels before pregnancy (T0), and LTG dosage and LTG plasma level changes in the first (T1), second (T2) and third trimester (T3), and post-partum (PP) as well as the sex of the foetus. Results: Reductions in the LTG concentration-to-dose ratio (C/D ratio) during pregnancy were seen in all genotype panels and varied between −53% and −74% in T3. Genetic polymorphism of UGT1A4 T142G (*3) and UGT2B7 C802T (*2) had the most pronounced influence on LTG clearance. Women with UGT1A4 142TG had a lower decrease in the C/D ratio in T3 than those with wild type: −53% (95%CI: −68% to −39%) versus −65% (95%CI: −69% to −60%) (p = 0.04). In homozygous carriers of UGT2B7 802TT the LTG C/D ratio was reduced significantly already in T1 (p = 0.015) as well as in T3 compared to the heterozygous carriers (802CT) (p = 0.04). Multiple regression analysis demonstrated that women who carried a female foetus had a significantly higher reductions in the LTG C/D ratio from T0 to the end of pregnancy than those with a male foetus (p = 0.003). In the univariate analysis the reductions in LTG C/D ratio were −64% in T2 (95%CI: −69% to −59%) and −67% in T3 (95%CI: −71% to −63%) in women who expected a female child compared to whose with a male child −58% in T2 (p = 0.002, 95%CI: −67% to −48%) and −57% in T3 (p < 0.001, 95%CI: −65% to −48%). Conclusion: Genetic polymorphism in UGT1A4 and UGT2B7 may play a modest role in LTG clearance changes during pregnancy. In addition, our study indicates that the sex of the foetus influenced significantly the change in LTG clearance.
AB - Objective: To evaluate the impact of maternal UGT1A4 and UGT2B7 genetic polymorphisms and sex of foetus on gestation-induced changes in lamotrigine (LTG) clearance during pregnancy and post-partum (PP). Methods: Single nucleotide polymorphisms UGT1A4 142T > G, L48V (*3), UGT1A4 70C > A, P24T (*2) and UGT2B7 802C > T, H268Y (*2) were determined in 40 women (47 pregnancies) with epilepsy treated with LTG. Retrospectively collected data included LTG dosage and LTG plasma levels before pregnancy (T0), and LTG dosage and LTG plasma level changes in the first (T1), second (T2) and third trimester (T3), and post-partum (PP) as well as the sex of the foetus. Results: Reductions in the LTG concentration-to-dose ratio (C/D ratio) during pregnancy were seen in all genotype panels and varied between −53% and −74% in T3. Genetic polymorphism of UGT1A4 T142G (*3) and UGT2B7 C802T (*2) had the most pronounced influence on LTG clearance. Women with UGT1A4 142TG had a lower decrease in the C/D ratio in T3 than those with wild type: −53% (95%CI: −68% to −39%) versus −65% (95%CI: −69% to −60%) (p = 0.04). In homozygous carriers of UGT2B7 802TT the LTG C/D ratio was reduced significantly already in T1 (p = 0.015) as well as in T3 compared to the heterozygous carriers (802CT) (p = 0.04). Multiple regression analysis demonstrated that women who carried a female foetus had a significantly higher reductions in the LTG C/D ratio from T0 to the end of pregnancy than those with a male foetus (p = 0.003). In the univariate analysis the reductions in LTG C/D ratio were −64% in T2 (95%CI: −69% to −59%) and −67% in T3 (95%CI: −71% to −63%) in women who expected a female child compared to whose with a male child −58% in T2 (p = 0.002, 95%CI: −67% to −48%) and −57% in T3 (p < 0.001, 95%CI: −65% to −48%). Conclusion: Genetic polymorphism in UGT1A4 and UGT2B7 may play a modest role in LTG clearance changes during pregnancy. In addition, our study indicates that the sex of the foetus influenced significantly the change in LTG clearance.
KW - Lamotrigine
KW - Polymorphism
KW - Pregnancy
KW - Sex of foetus
KW - UGT
U2 - 10.1016/j.eplepsyres.2018.01.011
DO - 10.1016/j.eplepsyres.2018.01.011
M3 - Journal article
C2 - 29395496
AN - SCOPUS:85041233108
VL - 140
SP - 199
EP - 208
JO - Journal of Epilepsy
JF - Journal of Epilepsy
SN - 0920-1211
ER -
ID: 213963937