Njajou, OT and Blackburn, EH and Pawlikowska, L and Mangino, M and Damcott, CM and Kwok, PY and Spector, TD and Newman, AB and Harris, TB and Cummings, SR and Cawthon, RM and Shuldiner, AR and Valdes, AM and Hsueh, WC
(2010)
A Common variant in the telomerase RNA component is associated with short telomere length.
PLoS ONE, 5 (9).
Abstract
Background: Telomeres shorten as cells divide. This shortening is compensated by the enzyme telomerase. We evaluated the effect of common variants in the telomerase RNA component (TERC) gene on telomere length (TL) in the populationbased Health Aging and Body Composition (Health ABC) Study and in two replication samples (the TwinsUK Study and the Amish Family Osteoporosis Study, AFOS). Methodology: Five variants were identified in the TERC region by sequence analysis and only one SNP was common (rs2293607, G/A). The frequency of the G allele was 0.26 and 0.07 in white and black, respectively. Testing for association between TL and rs2293607 was performed using linear regression models or variance component analysis conditioning on relatedness among subjects. Results: The adjusted mean TL was significantly shorter in 665 white carriers of the G allele compared to 887 non-carriers from the Health ABC Study (4.69±0.05 kbp vs. 4.86±0.04 kbp, measured by quantitative PCR, p = 0.005). This association was replicated in another white sample from the TwinsUK Study (6.90±0.03 kbp in 301 carriers compared to 7.06±0.03 kbp in 395 non-carriers, measured by Southern blots, p = 0.009). A similar pattern of association was observed in whites from the family-based AFOS and blacks from the Health ABC cohort, although not statistically significant, possibly due to the lower allele frequency in these populations. Combined analysis using 2,953 white subjects from 3 studies showed a significant association between TL and rs2293607 (β =-0.19±0.04 kbp, p = 0.001). Conclusion: Our study shows a significant association between a common variant in TERC and TL in humans, suggesting that TERC may play a role in telomere homeostasis. © 2010 Njajou et al.
Share
| Citation/Export: |
|
| Social Networking: |
|
Details
| Item Type: |
Article
|
| Status: |
Published |
| Creators/Authors: |
| Creators | Email | Pitt Username | ORCID  |
|---|
| Njajou, OT | | | | | Blackburn, EH | | | | | Pawlikowska, L | | | | | Mangino, M | | | | | Damcott, CM | | | | | Kwok, PY | | | | | Spector, TD | | | | | Newman, AB | ANEWMAN@pitt.edu | ANEWMAN | | | Harris, TB | | | | | Cummings, SR | | | | | Cawthon, RM | | | | | Shuldiner, AR | | | | | Valdes, AM | | | | | Hsueh, WC | | | |
|
| Contributors: |
| Contribution | Contributors Name | Email | Pitt Username | ORCID |
|---|
| Editor | Toland, Amanda Ewart | UNSPECIFIED | UNSPECIFIED | UNSPECIFIED |
|
| Date: |
1 November 2010 |
| Date Type: |
Publication |
| Journal or Publication Title: |
PLoS ONE |
| Volume: |
5 |
| Number: |
9 |
| DOI or Unique Handle: |
10.1371/journal.pone.0013048 |
| Schools and Programs: |
School of Public Health > Epidemiology |
| Refereed: |
Yes |
| MeSH Headings: |
Adolescent; Adult; Aged; Aged, 80 and over; Aging--genetics; Aging--metabolism; Body Composition; Cohort Studies; European Continental Ancestry Group--genetics; Female; Genetic Variation; Humans; Male; Middle Aged; Osteoporosis--genetics; Osteoporosis--metabolism; Polymorphism, Single Nucleotide; RNA--genetics; RNA--metabolism; Telomerase--genetics; Telomerase--metabolism; Telomere--genetics; Telomere--metabolism; Twins--genetics; Twins--metabolism; Young Adult |
| Other ID: |
NLM PMC2946401 |
| PubMed Central ID: |
PMC2946401 |
| PubMed ID: |
20885959 |
| Date Deposited: |
21 Aug 2012 14:25 |
| Last Modified: |
22 May 2019 12:55 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/13554 |
Metrics
Monthly Views for the past 3 years
Plum Analytics
Altmetric.com
Actions (login required)
 |
View Item |
![[img]](http://d-scholarship.pitt.edu/style/images/fileicons/text_plain.png)
![[feed]](/images/feed-icon-32x32.png){kind=icon}