Plm. Zusterzeel et al., Polymorphisms in biotransformation enzymes and the risk for recurrent early pregnancy loss, MOL HUM REP, 6(5), 2000, pp. 474-478
An imbalance between phase I drug metabolizing enzymes and phase II detoxif
ication enzymes may contribute to the development of pre-eclampsia. Polymor
phic variants in the phase I enzyme, cytochrome P450 genes may lead to incr
eased toxification, whereas polymorphisms in the phase II enzyme, glutathio
ne S-transferase genes may result in impaired detoxification, Most abundant
in placenta and decidua is glutathione S-transferase P1-1, which may there
fore be of particular importance in reproduction. We studied the frequencie
s of polymorphic variants in those enzymes in 187 women with recurrent earl
y pregnancy loss and in 109 women with an uncomplicated obstetric history.
DNA was extracted and subsequently polymerase chain reaction based genotypi
ng assays were used. chi(2)-Analysis and Fisher's exact test were used for
statistical evaluation. The glutathione S-transferase P1b-1b genotype was f
ound significantly more often in women with recurrent early pregnancy loss
than in controls (12% versus 5%, P = 0.03), in particular in those who cons
umed coffee (P = 0.02) or smoked cigarettes (P = 0.04). Polymorphisms in ot
her glutathione S-transferase and cytochrome P450 genes occurred equally fr
equently in cases and controls. In conclusion, the occurrence of the glutat
hione S-transferase P1b-1b genotype, leading to lower glutathione S-transfe
rase Pi enzyme activity and consequently to impaired placental detoxificati
on, may represent a risk factor for recurrent early pregnancy loss.