RT Journal Article
SR Electronic
T1 Telomere length is shorter in healthy offspring of subjects with coronary artery disease: support for the telomere hypothesis
JF Heart
JO Heart
FD BMJ Publishing Group Ltd and British Cardiovascular Society
SP 422
OP 425
DO 10.1136/hrt.2007.139675
VO 94
IS 4
A1 S W Brouilette
A1 A Whittaker
A1 S E Stevens
A1 P van der Harst
A1 A H Goodall
A1 N J Samani
YR 2008
UL http://heart.bmj.com/content/94/4/422.abstract
AB Background: Telomeres are shorter in subjects with coronary artery disease (CAD) and may indicate premature biological ageing. However, whether shorter telomeres are a primary abnormality or secondary to the disease is unclear.Objective: To investigate whether shorter telomeres are a primary abnormality or secondary to CAD, telomere lengths in healthy young adults with contrasting familial risk of CAD were compared.Design: Case–control study.Methods: Mean telomere restriction fragment (TRF) length in DNA from circulating leucocytes was determined by Southern blotting in 45 healthy offspring of subjects with premature CAD (case offspring) and 59 offspring from families without such a history (control offspring). Correlation in mean TRF length was also assessed in 67 offspring–parent pairs.Results: On average, a decrease of 27.5 (10.7) bp in mean TRF per year of age was found. The unadjusted mean TRF length was 6.34 kb (95% CI 6.13 to 6.55) for case offspring and 6.75 kb (95% CI 6.57 to 6.94) for offspring of controls (p = 0.004). The adjusted difference in mean TRF between case and control offspring was 472 bp (95% CI 253 to 691, p<0.001), equivalent to about 17 years of age-related attrition in telomere length. Furthermore, there was a significant positive correlation in mean TRF length between offspring and their parents (r = 0.37, p = 0.002).Conclusion: These findings suggest that inheritance of shorter telomeres is associated with increased familial risk of CAD. They support the hypothesis that telomere length is a primary abnormality involved in the pathogenesis of CAD.