UGT polymorphisms and epileptic seizure control in pregnant women treated with Lamotrigine

OBJECTIVE: We investigated whether polymorphisms of selected uridine-diphospho-glucuronosyl-tranferases (UGT) involved in Lamotrigine (LTG) metabolism are associated with seizure control during pregnancy and post-partum in women with epilepsy treated with LTG.

METHODS: Single nucleotide polymorphisms for UGT1A4 * 2 (P24T, c.70 C>A), UGT1A4 * 3 (L48V c.142 T > G) and UGT2B7 * 2 (H268Y, c.802 C>T), were determined in 47 pregnancies in 40 non-smoking women with LTG-treated epilepsy. Retrospectively collected data included seizure type and frequency, LTG dosage and LTG plasma level changes during pregnancy and PP. We evaluated the effect of UGT genotype on seizure control throughout pregnancy and post-partum (T1-PP).

RESULTS: In 47 pregnancies, seizure control was achieved in 60 % in T1-PP. Occurrence of seizures T1-PP was not directly associated with UGT genotype, but with having pre-pregnant seizures within the past 6 months (OR 8.33 (95 % CI 1.53-45.41, p = 0.01) and 12 months (OR 5.25, 95 % CI 1.47-18.77, p = 0.02) preceding pregnancy.

CONCLUSION: We did not observe any proximate effect of UGT genotypes on seizure control during pregnancy and post-partum in women treated with LTG, but seizures within the year preceding pregnancy had a significant impact.