Angiotensinogen gene M235T polymorphism predicts left ventricular hypertrophy in endurance athletes

J Am Coll Cardiol. 1999 Aug;34(2):494-9. doi: 10.1016/s0735-1097(99)00199-0.


Objectives: We studied whether left ventricular mass in athletes associates with polymorphisms in genes encoding components of the renin-angiotensin system.

Background: Adaptive left ventricular hypertrophy is a feature of the athlete's heart. However, similarly training athletes develop left ventricular mass to a different extent, suggesting that genetic factors may modulate heart size.

Methods: We measured left ventricular mass by echocardiography in 50 male and 30 female elite endurance athletes aged 25 +/- 4 (mean +/- SD) years. Deoxyribonucleic acid samples were prepared for genotyping of angiotensinogen (AGT) gene M235T polymorphism, angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and angiotensin II type 1 receptor (AT1) gene A1166C polymorphism.

Results: The AGT gene M235T genotypes were significantly associated with left ventricular mass independently of blood pressure in both genders (p = 0.0036 for pooled data). TT homozygotes had greater mass compared with MM homozygotes in both men (147 +/- 12 g/m vs. 132 +/- 15 g/m, p = 0.032) and women (121 +/- 12 g/m vs. 101 +/- 13 g/m, p = 0.019). There was a gender difference in the relation between myocardial mass and AGT genotype, MT heterozygotes resembling MM homozygotes among women and TT homozygotes among men. The other studied gene polymorphisms were not associated with left ventricular mass.

Conclusions: Angiotensinogen gene M235T polymorphism is associated with the variability in left ventricular hypertrophy induced by endurance training, with athletes homozygous for the T allele having the largest hearts. We found no association between ACE gene I/D or AT1 gene A1166C polymorphisms and left ventricular mass.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological / genetics*
  • Adult
  • Angiotensinogen / genetics*
  • Echocardiography
  • Female
  • Genetic Predisposition to Disease*
  • Genotype
  • Heterozygote
  • Homozygote
  • Humans
  • Hypertrophy, Left Ventricular / diagnostic imaging
  • Hypertrophy, Left Ventricular / genetics*
  • Male
  • Peptidyl-Dipeptidase A / genetics
  • Physical Endurance
  • Polymorphism, Genetic*
  • Receptors, Angiotensin / genetics
  • Sex Factors
  • Sports*


  • Receptors, Angiotensin
  • Angiotensinogen
  • Peptidyl-Dipeptidase A