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

Aims: There are controversies concerning the association of angiotensin-con verting enzyme (ACE) insertion/deletion (I/D) polymorphism with left ventri cular hypertrophy (LVH), and the unclear association between angiotensinoge n (ATG) M235T polymorphism and LVH, We investigated both the separate and i nteractive effects of these two genes on LVH in patients (N=396) with cardi ovascular disease and normal healthy volunteers (N=133). Results: Frequency of DD genotype of ACE gene was significantly (P<0.05) higher in patients w ith LVH than patients without LVH or normal controls. Frequency of TT genot ype of ATG gene in patients with LVH was significantly (P<0.01) greater tha n that in normal controls or marginally (P=0.1) higher than that in patient s without LVH, These findings were also observed in normotensive patients a nd normal controls after excluding hypertensive patients. Only in patient g roup, the frequency of DD genotype in the highest quartile of LVMI was sign ificantly greater than that in the lowest quartile (P<0.05). The higher ten dency of TT genotype in the highest quartile patients compared with that in the lowest, did not reach statistical significance. In combined genotype a nalysis, there was a remarkable difference in LVMI between the two extreme double homozygotes only in patient group (156 +/- 25 versus 109 +/- 25 g/m( 2) for TT + DD versus MM + II) (P<0.01). In ANCOVA, the interaction term co mposed of ACE and ATG genotype was a significant independent variable for L VMI only in the male patient group (P<0.01). Conclusion: The D-allele of AC E and T-allele of ATG gene exert a synergistic effect on cardiac hypertroph y in male patients with cardiovascular diseases, but not in normal healthy population. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.