Genetic and environmental factors associated with the development of hypertension in pregnancy

Hypertension in pregnancy (HP), one of the most common causes of perinatal deaths, is a multifactorial disease with genetic and environmental factors involved in its etiology. We have carried out molecular epidemiologic research with the purpose of (1) identifying gene variants associated with HIP in Japanese women, and (2) analyzing the genetic and environmental factors involved in the pathophysiology of the disease. Self-administered questionnaires were returned by the subjects between 1 and 6 months after delivery. The candidate genetic variants were identified by use of a PCR-RFLP method. T235 of AGT, C1166 of AT1 and Asp298 of NOS3 were respectively associated with HP, although no significant associations were found between the common genetic variants and HP in ACE, FV, MTHFR, B3AR, TNF-A, PAI-1, GSTP1, mEH, and LPL. In analyses using genetic, environmental and lifestyle factors, 5 factors before pregnancy and 4 factors during pregnancy were significantly associated with HIP in univariate analysis. Further multivariate analysis revealed 3 factors before pregnancy, i.e. "prepregnancy BMI 2: 24 kg/ml", "family history of hypertension" and "TT genotype of AGT', and 2 factors during pregnancy, i.e. "mentally stressful condition" and "salty dishes preferred". Dividing the subjects into 2 subgroups according to whether they possessed "TT genotype of AGT' or not, we identified acquired risk factors before and during pregnancy for HIP in each groups. The multivariate analysis identified "mentally stressful condition" as a potent significant risk factor during pregnancy in the former subgroup. However, there were no significant risk factors concerning and "mental stress" in the latter subgroup. Through further exploration of the risk factors associated with HIP, we hope to provide useful suggestions about the development of new and effective preventive measures for a range of multifactorial diseases.