Angiotensin-converting enzyme and angiotensinogen gene polymorphisms are non-randomly distributed in oral contraceptive-induced hypertension.

OBJECTIVES AND METHODS: Oral contraceptives (OC) usage increases serum angiotensinogen levels to three to five times normal and about 5% of these women develop arterial hypertension. The genetic contribution to this susceptibility to OC-induced hypertension is poorly understood. We have analyzed the genotypes of 149 hypertensive and 101 normotensive women using oral contraceptives, for three genetic polymorphisms in genes of the renin-angiotensin system: an insertion/deletion (I/ D) in the angiotensin converting enzyme (ACE) gene, the T235M polymorphism of the angiotensinogen gene (AGT) and a point mutation in its promoter. RESULTS: After cessation of oral contraception the mean arterial pressures of the hypertensive women were separable into two non-overlapping groups; 88 of the women remained hypertensive and 61 returned to normal blood pressure. Both groups of hypertensive women had a similarly higher frequency of hypertensive relatives than the normotensive women, but were otherwise similar. The 235T allele of AGT was significantly increased in frequency in the 61 oral contraceptive-inducible hypertensive women compared with the controls and the 88 women that remained hypertensive. The ACE I/D genotypes were similarly distributed within the three groups of women, but were distinctly non-random in the oral contraceptive-induced hypertensive women when they were also classified by AGT genotype. CONCLUSION: This statistical interaction of genotype frequencies suggests that the genetic basis of susceptibility to OC-induced hypertension is complex.

Relationship between birth weight and blood pressure in adolescence.

BACKGROUND: Several studies have found a relation ship between small size at birth and high blood pressure (HBP). However, this association has not been fully evaluated in adolescence. The aim of the present study was to evaluate the relation of birth weight (BW) to BP in adolescence, controlling for factors related to BP, to extrauterine environment, and to maternal risk of fetal distress. METHODS: In 1310 adolescents (ages 12-14 years), randomly selected from Turin school children, we evaluated BP, heart rate (HR), weight, height, familial risk of hypertension, parental cultural level, BW, and maternal history of diseases during pregnancy. The BW-BP association was tested by using multiple regression analysis and adjusting for the other variables mentioned above. The same analysis was done for the subgroup at high risk of fetal distress. RESULTS: The association between BW and BP was negative but weak when we adjusted for all confounders (= -0.07 in males; = -0.27 in females). The association was negative and became stronger after the inclusion of all confounders, particularly HR (= -3.92), in the group of children at high risk of fetal distress. CONCLUSIONS: Intrauterine environment, as reflected by BW, has little effect on BP in early adolescence without concomitant maternal diseases or environmental conditions leading to severe placental hypoperfusion.