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 Posted: Tue Oct 07, 2008 8:12 pm Post subject: A common variant of the p16(INK4a) genetic region is associa |
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Mech Ageing Dev. 2007 May-Jun;128(5-6):370-7. Epub 2007 Mar 27. Links
A common variant of the p16(INK4a) genetic region is associated with
physical function in older people.Melzer D, Frayling TM, Murray A,
Hurst AJ, Harries LW, Song H, Khaw K, Luben R, Surtees PG, Bandinelli
SS, Corsi AM, Ferrucci L, Guralnik JM, Wallace RB, Hattersley AT,
Pharoah PD.
Peninsula Medical School, RD&E Wonford Site, Barrack Road, Exeter EX2
5DW, UK. david.melzer@pms.ac.uk
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.
PMID: 17459456 [PubMed - indexed for MEDLINE]
PMCID: PMC2074888 |
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