Renin-angiotensin system polymorphisms and coronary events in familial hypercholesterolemia

The role of renin-angiotensin system polymorphisms as risk factors for coro nary heart disease (CHD) is controversial. This study investigated their ro le in patients with heterozygous familial hypercholesterolemia (FH). Polymo rphism frequencies for angiotensin-I- converting enzyme insertion/deletion (ACE I/D), angiotensinogen M235T, and angiotensin-II type I receptor (AG2R) A1166C were determined in 112 patients with FH and 72 patients with polyge nic hypercholesterolemia, of whom 26.7% and 41.6%, respectively, had establ ished CHD. None of the polymorphisms were associated with risk of CHD in pa tients with polygenic hypercholesterolemia in this study. Logistic regressi on analysis of risk factors for CHD in patients with FH identified male sex (odds ratio [OR] = 3.03; 95% CI, 3.07 to 3.72; P = 0.05), smoking (OR = 2, 91; 95% CI, 2.16 to 4.24; P = 0.05), diastolic blood pressure (OR = 3.70; 9 5% CI, 3.43 to 3.97; P = 0.02), plasma glucose (OR = 3.31; 95% CI, 3.10 to 3.52; P = 0.04), and the AG2R A1166C polymorphism as risk factors. The OR f or the AG2R A1166C polymorphism was 2.26 (95% CI, 1.26 to 3.72; P = 0.06) a nd-increased to 3.10 (95% CI, 1.20 to 7.52; P = 0.04) after adjustment for other risk factors. The AG2R A1166C polymorphism may interact with severe h ypercholesterolemia and other risk factors to increase risk of CHD in FH pa tients.