Year: 2012
Type: article
Study design: Observational Study
Abstract: 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.
Source: Aging Cell
Institutions: Emory University, National Institutes of Health, National Human Genome Research Institute, University of Pennsylvania, Boston University, Boston Medical Center, Albert Einstein College of Medicine, MultiMedica, Institute of Biomedical Technologies, National Research Council, University of Michigan
Language: English
Subfield: Aging
Domain: Life Sciences
Open Access status: bronze
Funders: Anatomical Society, National Institutes of Health, National Institute on Aging, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases
Awards: G1233934336, G301048564, G3160986405, G3288803086, G3458277176, G4498387036, G4701717143, G5331206282, G6086561418, G640430542, GENETIC FACTORS CAUSING LONGEVITY IN CENTENARIANS, G867105584, G9000018859, G9000034339, G9000086042, G9000285095, Michigan Diabetes Research Center (MDRC), Penn Dermatology Research Training Program, G909485966
OpenAlex ID: W2140399676