Susceptibility to Pre-Eclampsia Is Associated with Multiple Genetic Polymorphisms in Maternal Biotransformation Enzymes

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Abstract
Probably no single gene is responsible for pre-eclampsia, but the disease merely is the result of polymorphisms in several genes in association with environmental factors. We therefore studied the simultaneous occurrence of several genetic polymorphisms in biotransformation enzymes in women who had developed pre- eclampsia, either with or without the HELLP syndrome, in comparison with healthy controls. The results of two previous studies on genetic polymorphisms in glutathione S-transferases P1, M1 and T1, epoxide hydrolase (EPHX) and cytochrome P4501A1 (CYP1A1) in 167 women with a history of pre-eclampsia and in 110 controls were combined. chi(2) analyses were used for statistical evaluation of the number of polymorphisms between cases and controls. There was a significant association with the number of genetic polymorphisms in biotransformation enzymes, pointing at an increased toxification or decreased detoxification, in women with a history of pre-eclampsia, as compared to healthy controls (p < 0.001). Women withthe simultaneous occurrence of two or more genetic polymorphisms in the above-mentioned biotransformation enzymes, most probably resulting in a disturbed detoxification capacity, may be at increased risk for pre-eclampsia.