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

Citation
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
Citations number
36
Categorie Soggetti
Cell & Developmental Biology
Journal title
MOLECULAR HUMAN REPRODUCTION
ISSN journal
13609947 → ACNP
Volume
6
Issue
5
Year of publication
2000
Pages
474 - 478
Database
ISI
SICI code
1360-9947(200005)6:5<474:PIBEAT>2.0.ZU;2-Z
Abstract
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.