Methods:

Study participants:

We tested the rs1333049 polymorphism in a sample of 80 centenarians (39 men and 41 women aged 100-104; body mass index [BMI], 21.8±3.5kg/m2), 218 patients younger than 40 who experienced precocious AMI (165 men and 53 women, aged 24-39; BMI, 26.2±3.1kg/m2), and a control group of 258 healthy young volunteers (128 men and 120 women, aged 22-39; BMI, 22.7±3.8kg/m2). Part of the sample has been described previously. Centenarians did not have major age-related diseases (i.e., type 2 diabetes mellitus, severe cognitive impairment, clinically evident cancer, ischemic heart disease, liver or renal insufficiency, severe physical impairment), but some of them showed decreased visual or auditory acuity. Subjects with precocious AMI were nondiabetic patients younger than 40 who were consecutively recruited at the cardiology departments of Alessandro Manzoni Hospital, Lecco, Italy.Effect on Human Longevity. Data Analysis The study power was calculated using the StatMate software, version 2.0 (GraphPad Inc., San Diego, CA). A test for deviation from the Hardy-Weinberg equilibrium was performed. Table: Distribution of rs Genotype and Allele Frequency for Centenarians 1.133304 and Healthy Young Controls. Genotype Allele Study group n GG GC CC G C Centenarians 80 22 (25.0%) 42 (52.5%) 16 (22.5%) 86 (53.7%) 74 (46.3%) Healthy young controls 258 47 (18.2%) 132 (51.2%) 79 (30.6%) 226 (43.8%) 290 (56.2%). Longevity emerged from studies in humans. Mech Ageing Dev; : Gonos ES. Genetics of aging: Lessons from centenarians. Exp Gerontol; : Atzmon G, Rincon M, Rabizadeh P, Barzilai N. Biological evidence for inheritance of exceptional longevity. Mech Ageing Dev; : Heijmans BT, Westendorp RG, Slagboom PE. Common gene variants, mortality and extreme longevity in humans. Exp Gerontol; : Helgadottir A, Thorleifsson G, Manolescu A, Gretarsdottir S, Blondal T, Jonasdottir A, Jonasdottir A, Sigurdsson A, Baker A, Palsson A, Masson G, Gudbjartsson DF, Magnusson KP, Andersen K, Levey AI, Backman VM, Matthiasdottir S, Jonsdottir T, Palsson S, Einarsdottir H, Gunnarsdottir S, Gylfason A, Vaccarino V, Hooper WC, Reilly MP, Granger CB, Austin H, Rader DJ, Shah SH, Quyyumi AA, Gulcher JR, Thorgeirsson G, Thorsteinsdottir U, Kong A, Stefansson K. A common variant on chromosome p affects the risk of myocardial infarction. Science; : Abdullah KG, Li L, Shen GQ, Hu Y, Yang Y, Ma inlay KG, Topol EJ, Wang QK. Four SNPs on chromosome p confer risk to premature, familial CAD and MI in an American Caucasian population (GenQuest). Ann Hum Genet; : Shen GQ, Li L, Rao S, Abdullah KG, Ban JM, Lee BS, Park JE, Wang QK. Four SNPs on chromosome p in a South Korean population implicate a genetic locus that confers high cross-race risk for development of coronary artery disease. Arterioscler Thromb Vasc Biol; : Chen Z, Qian Q, Ma G, Wang J, Zhang X, Feng Y, Shen C, Yao Y. A common variant on chromosome p affects the risk of early-onset coronary artery disease. Mol Biol Rep; : Shen GQ, Rao S, Martinelli N, Li L, Olivieri O, Corrocher R, Abdullah KG, Hazen SL, Smith J, Barnard J,
Plow EF, Girelli D and Wang QK. Association between four SNPs on chromosome p and myocardial infarction is replicated in an Italian population. J Hum Genet; : Helgadottir A,
Thorleifsson G,
Magnusson KP,
Gretarsdottir S,
Steinthorsdottir V,
Manolescu A,
Jones GT,
Rinkel GJ,
Blankensteijn JD,
Ronkainen A,
Jaaskelainen JE,
Kyo Y,
Lenk GM,
Sakalihasan N,
Kostulas K,
Gottsater A,
Flex A,
Stefansson H,
Hansen T,
Andersen G,
Weinsheimer S,
Borch-Johnsen K,
Jorgensen T,
Shah SH,
Quyyumi AA,
Granger CB,
Reilly MP,
Austin H,
Levey AI,
Vaccarino V,
Palsdottir E,
Walters GB, Jonsdottir T, Snorradottir S, Magnusdottir D, Gudmundsson G, Ferrell RE, Sveinbjornsdottir S, Hernesniemi J, Niemela M, Limet R, Andersen K, Sigurdsson G, Benediktsson R, Verhoeven EL, Teijink JA, Grobbee DE, Rader DJ, Collier DA, Pedersen O, Pola R, Hillert J, Lindblad B, Valdimarsson EM, Magnadottir HB, WijmTomoike H, Goto Y, Nonogi H, Takahashi R, Iwai N. Validation of the association of genetic variants on chromosomes p and q with myocardial infarction in a Japanese population. Circ J; :. Hunter DJ, Khoury MJ, Drazen JM. Letting the genome out of the bottle - will we get our wish? N Engl J Med; :. Farzaneh-Far R, Na B, Schiller NB, Whooley MA. Lack of association of chromosome p genotype with cardiovascular structure and function in persons with stable coronary artery disease: The Heart and Soul Study. Atherosclerosis; :. Geroldi D, Falcone C, Minoretti P, Emanuele E, Arra M, D'Angelo A. High levels of soluble receptor for advanced glycation end products may be a marker of extreme longevity in humans. J Am Geriatr Soc; :. Bostock CV, Soiza RL, Whalley LJ. Genetic determinants of ageing processes and diseases in later life. Maturitas; :. Karvanen J, Silander K, Kee F, Tiret L, Salomaa V, Kuulasmaa K, Wiklund PG, Virtamo J, Saarela O, Perret C, Perola M, Peltonen L, Cambien F, Erdmann J, Samani NJ, Schunkert H, Evans A; MORGAM Project. The impact of newly identified loci on coronary heart disease, stroke and total mortality in the MORGAM prospective cohorts. Genet Epidemiol; :. Liu Y, Sanoff HK, Cho H, Burd CE, Torrice C, Mohlke KL, Ibrahim JG, Thomas NE and Sharpless NE. INK4a/ARF transcript expression is associated with chromosome p variants linked to atherosclerosis. PLoS One; :e.