Interethnic differences in coronary heart disease mortality in 25 populations: association with the angiotensin-converting enzyme DD genotype frequency

BACKGROUND: Despite changes in dietary habits and steadily increasing serum cholesterol concentrations, coronary heart disease (CHD) mortality rates in developed South-East Asian populations are still one quarter those in many Western populations. We propose that genetic factors may, in part, contribute to these differences in CHD mortality.

DESIGN: Using an ecological study design, we have investigated the comparative roles of serum cholesterol concentration and the angiotensin-converting enzyme (ACE) homozygote deletion (DD) genotype frequency, which has recently been implicated in CHD mortality.

METHODS: Using our genotyping data from local Chinese populations, together with previously published data on ACE gene frequency and cholesterol concentrations, we correlated ACE DD genotype frequencies and mean serum cholesterol concentrations with World Health Organization age-adjusted CHD mortality rates in 25 ethnically diverse populations.

RESULTS: Although mean serum cholesterol accounted for 67% of the variance in CHD mortality rates for all populations (r=0.82, 95% Cl 0.63-0.92, n=25, P<0.001), the ACE DD frequency accounted for 61% of the variance in 'low' cholesterol populations (r=0.78, 95% Cl 0.43-0.91, n= 14, P<0.001) with no additional contribution from serum cholesterol concentration. Moreover, in the 'low' cholesterol population, mean serum cholesterol accounted for only 37% of the variance.

CONCLUSION: We hypothesize that differences in the frequency of the ACE DD genotype in populations with low mean serum cholesterol concentrations may play some part in determining interethnic differences in CHD mortality rates.