Synergistic effect of angiotensin-converting enzyme and angiotensinogen gene on cardiac hypertrophy

Aims: There are controversies concerning the association of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism with left ventricular hypertrophy (LVH), and the unclear association between angiotensinogen (ATG) M235T polymorphism and LVH. We investigated both the separate and interactive effects of these two genes on LVH in patients (N=396) with cardiovascular disease and normal healthy volunteers (N=133). Results: Frequency of DD genotype of ACE gene was significantly (P<0.05) higher in patients with LVH than patients without LVH or normal controls. Frequency of TT genotype of ATG gene in patients with LVH was significantly (P<0.01) greater than that in normal controls or marginally (P=0.1) higher than that in patients without LVH. These findings were also observed in normotensive patients and normal controls after excluding hypertensive patients. Only in patient group, the frequency of DD genotype in the highest quartile of LVMI was significantly greater than that in the lowest quartile (P<0.05). The higher tendency of TT genotype in the highest quartile patients compared with that in the lowest, did not reach statistical significance. In combined genotype analysis, there was a remarkable difference in LVMI between the two extreme double homozygotes only in patient group (156±25 versus 109±25 g/m2 for TT+DD versus MM+II) (P<0.01). In ANCOVA, the interaction term composed of ACE and ATG genotype was a significant independent variable for LVMI only in the male patient group (P<0.01). Conclusion: The D-allele of ACE and T-allele of ATG gene exert a synergistic effect on cardiac hypertrophy in male patients with cardiovascular diseases, but not in normal healthy population.