Telomere length is shorter in healthy offspring of subjects with coronary artery disease: support for the telomere hypothesis
Abstract
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.
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Inter-individual variation in mean leukocyte telomere length (LTL) is associated with cancer and several age-associated diseases.
“Inter-individual variation in mean leukocyte telomere length (LTL) is associated with cancer and several age-associated diseases.”
From Identification of seven loci affecting mean telomere length and their association with disease (2013) · cites this paper as [13]
In cross-sectional population studies, mean LTL is longer in women than in men and is inversely associated with age, declining by between 20-40 base pairs per year.
“In cross-sectional population studies mean LTL is longer in women than in men and is inversely associated with age (declining by between 20–40 base-pairs (bp) per year)9, 12–14.”
From Identification of seven loci affecting mean telomere length and their association with disease (2013) · cites this paper as [13]
Shorter age-and sex-adjusted mean LTL has been found to be associated with risk of several age-related diseases, including CAD.
“Furthermore, shorter age-and sex-adjusted mean LTL has been found to be associated with risk of several age-related diseases, including CAD12–15 and has been advanced as a marker of biological ageing16.”
From Identification of seven loci affecting mean telomere length and their association with disease (2013) · cites this paper as [13]
Many prior studies using Southern blotting have shown that mean LTL attrition rate is about ~30 bp per year.
“However, many prior studies that have used Southern blotting to measure LTL have shown that mean LTL attrition rate is about ~30 bp per year8, 12–14, 25.”
From Identification of seven loci affecting mean telomere length and their association with disease (2013) · cites this paper as [13]
One of the most widely reported associations for LTL to date has been that between shorter mean LTL and CAD.
“One of the most widely reported associations for LTL to date has been that between shorter mean LTL and CAD12–14, 25.”
From Identification of seven loci affecting mean telomere length and their association with disease (2013) · cites this paper as [13]
The finding is consistent with the prospective WOSCOPS study where, after adjustment for other CAD risk factors, baseline LTL was associated with a 44% higher risk of CAD over the ensuing mean 5.5 years of follow-up in individuals in the tertile with the shortest LTL compared with the longest LTL.
“Nonetheless, the finding is consistent with that in the prospective WOSCOPS study where, after adjustment for other CAD risk factors, baseline LTL was associated with a 44% higher risk of CAD over the ensuing mean 5.5 years of follow-up in individuals in the tertile with the shortest LTL compared with the longest LTL13.”
From Identification of seven loci affecting mean telomere length and their association with disease (2013) · cites this paper as [13]
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Identification of seven loci affecting mean telomere length and their association with disease
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- Authors
- Brouilette, S. W., Whittaker, A., Stevens, S. E., van der Harst, P., Goodall, A. H., & Samani, N. J.
- Affiliations
- University of Leicester (GB)
- Corresponding author
- Samani, N J
- Venue
- Heart
- Publisher
- BMJ
- Published
- 2008-03-17
- Volume
- 94
- Issue
- 4
- Pages
- 422-425
- ISSN
- 1355-6037 (ISSN-L)
- 1468-201X
- OpenAlex
- W2135274167
- Cited by
- 96
- References
- 26
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 4 · 2020: 5 · 2019: 2 · 2018: 3 · 2017: 5 · 2016: 3 · 2015: 5 · 2014: 8 · 2013: 10 · 2012: 5
- FWCI
- 8.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Heart (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
- Leicester Research Archive (University of Leicester) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Funders
- British Heart Foundation
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- telomere length, coronary artery disease, familial risk, telomere restriction fragments, genetic inheritance
- MeSH terms
- Adult, Coronary Artery Disease, Female, Humans, Male, Polymorphism, Restriction Fragment Length, Case-Control Studies, Telomere, Genetic Predisposition to Disease
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