Polymorphisms in biotransformation enzymes and the risk for recurrent early pregnancy loss

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.