Journal article
A common variant of the p16 INK4a genetic region is associated with physical function in older people
Mechanisms of ageing and development, Vol.128(5), pp.370-377
2007
DOI: 10.1016/j.mad.2007.03.005
PMCID: PMC2074888
PMID: 17459456
Abstract
p16
INK4a is active in cell senescence, ageing and tumor suppression. Deletion of the small p16
INK4a/ARF/p15
INK4b region occurs in many cancers. We screened 25 common polymorphisms across the region and three related genes for associations with physical functioning in older people.
In an initial sample of 938 (aged 65–80 years) from the EPIC study (Norfolk, UK), the rs2811712 SNP minor allele (located between the shared p16
INK4a/ARF locus and p15
INK4b) was associated with reduced physical impairment. This association remained after testing an additional 1319 EPIC-Norfolk samples (
p-value
=
0.013, total
n
=
2257), and on independent replication in the InCHIANTI study (
n
=
709,
p
=
0.015), and at one-sided significance in Iowa-EPESE (
n
=
419,
p
=
0.079). Overall (
n
=
3372), the prevalence of severely limited physical function was 15.0% in common homozygotes and 7.0% in rare homozygotes (per minor allele odds ratio
=
1.48, 95% CI: 1.17–1.88,
p
=
0.001, adjusted for age, sex and study). This estimate was similar excluding screening set 1 (OR
=
1.45, 95% CI: 1.09–1.92,
p
=
0.010,
n
=
2434).
These findings require further replication, but provide the first direct evidence that the p16
INK4a/ARF/p15
INK4b genetic region and the senescence machinery are active in physical ageing in heterogeneous human populations. The mechanism involved may be via greater cellular restorative activity and reduced stem cell senescence.
Details
- Title: Subtitle
- A common variant of the p16 INK4a genetic region is associated with physical function in older people
- Creators
- David Melzer - Royal Devon and Exeter HospitalTimothy M. Frayling - Royal Devon and Exeter HospitalAnna Murray - Royal Devon and Exeter HospitalAlison J. Hurst - Royal Devon and Exeter HospitalLorna W. Harries - Royal Devon and Exeter HospitalHonglin Song - University of CambridgeKayTee Khaw - University of CambridgeRobert Luben - University of CambridgePaul G. Surtees - University of CambridgeStefania S. Bandinelli - National Research CouncilAnna-Maria Corsi - University of FlorenceLuigi Ferrucci - National Institute on AgingJack M. Guralnik - National Institute on AgingRobert B. Wallace - University of IowaAndrew T. Hattersley - Royal Devon and Exeter HospitalPaul D. Pharoah - University of Cambridge
- Resource Type
- Journal article
- Publication Details
- Mechanisms of ageing and development, Vol.128(5), pp.370-377
- DOI
- 10.1016/j.mad.2007.03.005
- PMID
- 17459456
- PMCID
- PMC2074888
- NLM abbreviation
- Mech Ageing Dev
- ISSN
- 0047-6374
- eISSN
- 1872-6216
- Publisher
- Elsevier Ireland Ltd
- Language
- English
- Date published
- 2007
- Academic Unit
- Epidemiology; Injury Prevention Research Center; Internal Medicine
- Record Identifier
- 9984363638502771
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