COC use, ACE/AGT gene polymorphisms, and risk of stroke

OBJECTIVES: To clarify the effects of the association between combined oral contraceptives (COC) use and ACE/AGT gene on stroke risk, and to undertake a preliminarily study of the molecular mechanism of the association between COC exposure and predisposing genes of hypertension on the increased risk of stroke. METHODS: This study was a multi-center case-control study based on the population of 25 towns in the surveillance regions of Jiangsu province, China. RESULTS: (i) The univariate analysis of the frequency of the DD genotype of ACE insert/delete (I/D) polymorphism between the cases and controls indicated its significant association with the stroke (P<0.01), especially for hemorrhagic stroke (P<0.01). (ii) Women with COC exposure and ACE I/D genotype had an increased risk for all strokes [adjusted odds ratio 5.63; 95% confidence interval (CI), 2.20, 15.68], and an increased risk for hemorrhagic stroke (adjusted odds ratio 31.53; 95% CI, 3.54, 281.14) after adjustment for education and occupation. (iii) Multivariate analyses showed that hypertension was the most important risk factor for hemorrhagic stroke and ischemic stroke. COC use was a significant risk factor for hemorrhagic stroke. The combined effects of COC use, for 15 years and above, and ACE I/D polymorphism increased the risk of all strokes by more than eight times, and the risk of hemorrhagic stroke by more than 15 times. CONCLUSION: Hypertension was a most important risk factor for stroke incidence. The D allele of ACE I/D polymorphism may be a potential risk allele for stroke. COC users carried the ID+DD genotype that may further increase the risk of stroke, especially for hemorrhagic stroke.