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 angi otensinogen levels to three to five times normal and about 5% of these wome n develop arterial hypertension. The genetic contribution to this susceptib ility to OC-induced hypertension is poorly understood. We have analyzed the genotypes of 149 hypertensive and 101 normotensive women using oral contra ceptives, 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 p oint 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; 8 8 of the women remained hypertensive and 61 returned to normal blood pressu re. Both groups of hypertensive women had a similarly higher frequency of h ypertensive relatives than the normotensive women, but were otherwise simil ar. The 235T allele of AGT was significantly increased in frequency in the 61 oral contraceptive-inducible hypertensive women compared with the contro ls 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 t hat the genetic basis of susceptibility to OC-induced hypertension is compl ex. Lippincott Williams & Wilkins.