Polymorphisms in biotransformation enzymes and the risk for recurrent early pregnancy loss.
An imbalance between phase I drug metabolizing enzymes and phase II detoxification enzymes may contribute to the development of pre-eclampsia. Polymorphic variants in the phase I enzyme, cytochrome P450 genes may lead to increased toxification, whereas polymorphisms in the phase II enzyme, glutathione S-transferase genes may result in impaired detoxification. Most abundant in placenta and decidua is glutathione S-transferase P1-1, which may therefore be of particular importance in reproduction. We studied the frequencies of polymorphic variants in those enzymes in 187 women with recurrent early pregnancy loss and in 109 women with an uncomplicated obstetric history. DNA was extracted and subsequently polymerase chain reaction based genotyping assays were used. chi(2)-Analysis and Fisher's exact test were used for statistical evaluation. The glutathione S-transferase P1b-1b genotype was found significantly more often in women with recurrent early pregnancy loss than in controls (12% versus 5%, P = 0.03), in particular in those who consumed coffee (P = 0.02) or smoked cigarettes (P = 0.04). Polymorphisms in other glutathione S-transferase and cytochrome P450 genes occurred equally frequently in cases and controls. In conclusion, the occurrence of the glutathione S-transferase P1b-1b genotype, leading to lower glutathione S-transferase Pi enzyme activity and consequently to impaired placental detoxification, may represent a risk factor for recurrent early pregnancy loss.
Zusterzeel
P L
PL
Departments of Obstetrics and Gynaecology, Gastroenterology and Pediatrics, University Hospital Nijmegen, St Radboud, The Netherlands.
Nelen
W L
WL
Roelofs
H M
HM
Peters
W H
WH
Blom
H J
HJ
Steegers
E A
EA
D000026:Abortion, Habitual / Q000235:genetics*; D000328:Adult; D016022:Case-Control Studies; D003069:Coffee; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008423:Maternal Age; D008875:Middle Aged; D009426:Netherlands; D011110:Polymorphism, Genetic; D011247:Pregnancy; D012907:Smoking
D003069:Coffee; D019363:Cytochrome P-450 CYP1A1; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1