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Angiotensinogen gene polymorphism in Japanese patients with hypertrophic cardiomyopathy
A Ishanov1, H Okamoto, K Yoneya
1Department of Cardiovascular Medicine, Hokkaido University School of Medicine, Kita-ku, Sapporo, Japan.
Insights
Genetic variations in the angiotensinogen gene may predispose individuals to hypertrophic cardiomyopathy (HCM). The T235 variant of angiotensinogen appears to increase the risk of developing HCM, particularly in sporadic cases.
Area of Science:
- Cardiovascular Genetics
- Molecular Cardiology
- Human Genetics
Background:
- Hypertrophic cardiomyopathy (HCM) is a complex cardiac condition with both genetic and environmental influences.
- The renin-angiotensin system (RAS) plays a crucial role in cardiovascular regulation and has been implicated in cardiac hypertrophy.
Purpose of the Study:
- To investigate the association between the angiotensinogen (AGT) gene and hypertrophic cardiomyopathy (HCM).
- To determine if specific genetic variants of the AGT gene contribute to the risk of developing HCM, especially in sporadic cases.
Main Methods:
- Genotyping of the angiotensinogen (AGT) gene, specifically the M235T polymorphism, using polymerase chain reaction (PCR) and allele-specific oligonucleotide primers.
- Comparison of allele frequencies in patients with HCM (familial and sporadic), their unaffected relatives, and healthy control subjects.
Main Results:
- The T allele frequency of the AGT gene was significantly higher in patients with sporadic HCM compared to unaffected relatives (88% vs 78%, p < 0.05).
- Conversely, the M allele frequency was higher in unaffected relatives than in sporadic HCM patients (23% vs 12%, p < 0.05).
- The T allele frequency in unaffected relatives was similar to that in healthy controls, suggesting a specific association with sporadic HCM.
Conclusions:
- Genetic predisposition plays a role in the development of HCM, particularly in sporadic forms.
- The T235 molecular variant of angiotensinogen (AGT) is identified as a potential predisposing factor for cardiac hypertrophy in HCM, associated with an approximately twofold increased risk.
Abstract:
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.