Human longevity and common variations in the LMNA gene: a meta-analysis.
| Autor: | Conneely KN; Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA. kconnee@emory.edu, Capell BC, Erdos MR, Sebastiani P, Solovieff N, Swift AJ, Baldwin CT, Budagov T, Barzilai N, Atzmon G, Puca AA, Perls TT, Geesaman BJ, Boehnke M, Collins FS |
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| Jazyk: | angličtina |
| Zdroj: | Aging cell [Aging Cell] 2012 Jun; Vol. 11 (3), pp. 475-81. Date of Electronic Publication: 2012 Mar 27. |
| DOI: | 10.1111/j.1474-9726.2012.00808.x |
| Abstrakt: | A mutation in the LMNA gene is responsible for the most dramatic form of premature aging, Hutchinson-Gilford progeria syndrome (HGPS). Several recent studies have suggested that protein products of this gene might have a role in normal physiological cellular senescence. To explore further LMNA's possible role in normal aging, we genotyped 16 SNPs over a span of 75.4 kb of the LMNA gene on a sample of long-lived individuals (LLI) (US Caucasians with age ≥ 95 years, N=873) and genetically matched younger controls (N=443). We tested all common nonredundant haplotypes (frequency ≥ 0.05) based on subgroups of these 16 SNPs for association with longevity. The most significant haplotype, based on four SNPs, remained significant after adjustment for multiple testing (OR=1.56, P=2.5 × 10(-5) , multiple-testing-adjusted P=0.0045). To attempt to replicate these results, we genotyped 3619 subjects from four independent samples of LLI and control subjects from (i) the New England Centenarian Study (NECS) (N=738), (ii) the Southern Italian Centenarian Study (SICS) (N=905), (iii) France (N=1103), and (iv) the Einstein Ashkenazi Longevity Study (N= 702). We replicated the association with the most significant haplotype from our initial analysis in the NECS sample (OR=1.60, P=0.0023), but not in the other three samples (P > 0.15). In a meta-analysis combining all five samples, the best haplotype remained significantly associated with longevity after adjustment for multiple testing in the initial and follow-up samples (OR=1.18, P=7.5 × 10(-4) , multiple-testing-adjusted P=0.037). These results suggest that LMNA variants may play a role in human lifespan. (© 2012 The Authors. Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.) |
| Databáze: | MEDLINE |
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