Angiotensinogen gene polymorphism in Japanese patients with hypertrophic cardiomyopathy.
To examine the contribution of the renin-angiotensin system to hypertrophic cardiomyopathy (HCM), we 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 (LVH) who were frequency matched to cases by age and sex. Patients were divided into familial or sporadic HCM (FHCM or SHCM) groups with or without affected members of their family. The region of interest in the angiotensinogen (AGT) gene, the missense mutation with methione-to-threonine amino acid substitution at codon 235 in angiotensinogen (M235T), was amplified by polymerase chain reaction with the use of allele-specific oligonucleotide primers flanking the polymorphic region of the AGT gene to amplify template deoxyribonucleic acid prepared from peripheral leukocytes. The T allele frequency was higher in the SHCM group than in unaffected siblings and offspring (88% vs 78%, X2 = 4.6, p < 0.05). The M allele frequency was higher in unaffected siblings and offspring than in patients with SHCM (23% vs 12%, X2 = 4.6, p < 0.05). The T allele frequency among unaffected siblings and offspring was similar to that observed in healthy subjects (78% vs 78%). We conclude that HCM, especially in sporadic cases, is partially determined by genetic disposition. The molecular variant of angiotensinogen T235 seems to be a predisposing factor for cardiac hypertrophy in HCM and carries an approximately twofold increased risk.
Ishanov
A
A
Department of Cardiovascular Medicine, Hokkaido University School of Medicine, Kita-ku, Sapporo, Japan.
Okamoto
H
H
Yoneya
K
K
Watanabe
M
M
Nakagawa
I
I
Machida
M
M
Onozuka
H
H
Mikami
T
T
Kawaguchi
H
H
Hata
A
A
Kondo
K
K
Kitabatake
A
A
D000328:Adult; D000483:Alleles; D000808:Angiotensinogen / Q000235:genetics*; D001483:Base Sequence; D002312:Cardiomyopathy, Hypertrophic / Q000208:ethnology / Q000235:genetics*; D017931:DNA Primers; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic / Q000235:genetics*
D017931:DNA Primers; D000808:Angiotensinogen