Abstract for presentation at 11th International Congress of Human Genetics

Association of the androgen receptor gene (CAG)n repeat region with severity of left ventricular hypertrophy in males with hypertrophic cardiomyopathy

  • Joanne Lind, Agnes Ginges Centre for Molecular Cardiology, Centenary Institute, Australia
  • Ms Christine Chiu, Agnes Ginges Centre for Molecular Cardiology, Centenary Institute, Australia
  • Ms Jodie Ingles, Agnes Ginges Centre for Molecular Cardiology, Centenary Institute, Australia
  • Dr Alison Heather, Gene Regulation Group, The Heart Research Institute, Australia
  • A/Prof Christopher Semsarian, Agnes Ginges Centre for Molecular Cardiology, Centenary Institute & Dept of Cardiology, Royal Prince Alfred Hospital, NSW, Australia

    • Purpose: Hypertrophic Cardiomyopathy (HCM) is an autosomal dominant disorder characterised by marked thickening of the left ventricular wall. Gender is known to be a risk factor in the incidence and severity of HCM, with males developing more severe disease. We sought to investigate an association between the length of the (CAG)n repeat region in the androgen receptor (AR) gene, with the severity of hypertrophy in HCM patients.
    Methods: Patients referred to the HCM clinic at RPAH, Sydney, with definite HCM and aged > 16yrs, were included in this study. Left ventricular hypertrophy was evaluated by 2D and M mode echocardiography and maximal left ventricular wall thickness (LVWT) measured. Genomic DNA was extracted from blood and PCR was performed to amplify the (CAG)n repeat region in exon 1 of the AR gene. Fragment length was determined using GeneScan. Linear regression was applied to determine the association between LVWT and number of CAG repeats, in males and females.
    Results: A total of 210 HCM probands, 128 males and 82 females, were studied. The mean LVWT was not significantly different between males (21.4±0.5mm) and females (20.7±0.7mm). The mean number of CAG repeats was 21.8 in both males (range 15-29) and females (range 13-30). A significant association was found between the number of CAG repeats and the extent of hypertrophy in males (P=0.007). For every increase of one repeat unit, wall thickness decreased by 0.5mm. There was no association between CAG repeat length and hypertrophy in females.
    Conclusion: The length of the (CAG)n repeat region is inversely associated with the severity of hypertrophy in male HCM patients. The length of the repeat region has previously been shown to be inversely associated with AR activity. The level of AR activity may be important in the development and progression of hypertrophy in male HCM patients. Understanding the role of androgens in HCM pathogenesis is likely to improve diagnosis and clinical management.

    Conference Organiser - ICMS Pty Ltd