Angiotensin-converting enzyme and angiotensinogen gene polymorphism in hypertrophic cardiomyopathy.

To examine the contribution of the renin-angiotensin system to hypertrophic cardiomyopathy (HCM), the authors studied 96 patients with HCM (mean age 50 years, 55% male), 105 of their unaffected siblings and offspring, and 160 healthy subjects without known hypertension and left ventricular hypertrophy who were frequency matched by age and sex. Patients were divided into familial or sporadic HCM (FHCM or SHCM) groups with or without affected family members. The T allele frequency was higher in the SHCM group than in unaffected siblings and offspring (88% versus 78%, chi(2)=4.6, P<0.05). The M allele frequency was higher in unaffected siblings and offspring than in patients with SHCM (23% versus 12%, chi(2)=4.6, P<0.05). The T allele frequency among unaffected siblings and offspring was similar to that observed in healthy subjects (78% versus 78%). The molecular variant of angiotensinogen T235 seems to be a predisposing factor for cardiac hypertrophy in HCM and carries an approximately twofold increased risk. The authors also determined angiotensin-converting enzyme gene insertion/deletion polymorphism. The D allele frequency was higher in SHCM than in FHCM. The findings suggest that HCM, especially in solitary cases, is partially determined by genetic disposition. These results also suggest that angiotensin-converting enzyme and angiotensinogen gene polymorphism are genetic contributing factors associated with cardiac hypertrophy in HCM.