Association between a Variant of the Glutathione S-Transferase P1 Gene (GSTP1) and Hypertension in Pregnancy in Japanese: Interaction with Parity, Age, and Genetic Factors

Hypertension in pregnancy (HP), including preeclampsia (PE), is known to be a multifactorial disease. Recently, an Ile105Val variant of the glutathione S-transferase P1 gene ( GSTP1) was shown to be associated with PE in The Netherlands. We therefore performed an association study of the Ile105Val variant comparing 131 patients with HP and 327 normal pregnant controls in Japan. We analyzed the data in the context of other risk factors before pregnancy. The frequency of the Ile/Val+Val/Val genotype of the GSTP1 was not significantly different between the HP (26%) patients and the controls (28%). However, in primiparous patients, the frequency was significantly different in elderly pregnancy (63% in severe HP vs. 18% in controls; P < 0.05), in the subgroup with the MM+MT genotypes of the angiotensinogen gene (50% in severe HP vs. 26% in controls; P < 0.05), and in the subgroup with the GA+AA genotypes of the endothelial nitric oxide synthase gene (42% in severe HP vs. 13% in controls; P < 0.05). These results suggest that this variant of the GSTP1 may play a role in the manifestation of HP together with other independently and/or synergistically acting factors, particularly in primiparous pregnancy.