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Heijmans BT, Westendorp RG, Slagboom PE. Common gene variants, mortality and extreme longevity in humans. Exp Gerontol

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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

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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 (Gen

uest). Ann Hum Genet

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Shen GQ, Li L, Rao S, Abdullah KG, Ban JM, Lee BS, Park JE, Wang QK. Four SNPs on chromosome

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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

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Chen Z, Qian Q, Ma G, Wang J, Zhang X, Feng Y, Shen C, Yao Y. A common variant on chromosome

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affects the risk of early-onset coronary artery disease. Mol Biol Rep

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Shen GQ, Rao S, Martinelli N, Li L, Olivieri O, Corrocher R, Abdullah KG, Hazen SL, Smith J, Barnard J, Plow EF, Girelli D, Wang QK. Association between four SNPs on chromo- some

p

and myocardial infarction is replicated in an Italian population. J Hum Genet

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Helgadottir A, Thorleifsson G, Magnusson KP, Gre´tarsdottir S, Steinthorsdottir V, Manolescu A, Jones GT, Rinkel GJ, Blankensteijn JD, Ronkainen A, Ja¨a¨skela¨inen JE, Kyo Y, Lenk GM, Sakalihasan N, Kostulas K, Gottsa¨ter A, Flex A, Ste- fansson 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, Hernes- niemi 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, Wijmenga C, Tromp G, Baas AF, Ruigrok YM, van Rij AM, Kuivaniemi H, Powell JT, Matthiasson SE, Gulcher JR, Thorgeirsson G, Kong A, Thorsteinsdottir U, Stefansson K. The same sequence variant on

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associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm. Nat Genet

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Matarin M, Brown WM, Singleton A, Hardy JA, Meschia JF, ISGS investigators. Whole genome analyses suggest ischemic stroke and heart disease share an association with polymor- phisms on chromosome

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Stroke

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Emanuele E, Lista S, Ghidoni R, Binetti G, Cereda C, Benussi L, Maletta R, Bruni AC, Politi P. Chromosome

p

The chromosomal region 9p21.3 has been identified in genome-wide association studies as a major susceptibility locus for the development of CAD.7,13 The association of this locus and its leading variant rs1333049 with CAD has been repeatedly and independently replicated.15–17 Other studies additionally proposed that the rs1333049 polymorphism at 9p21.3 is associated with a number of other age-related dis- orders, including stroke22 and dementia.14 Although the molecular mechanisms behind these associations are un- known, we reasoned that if the C allele of rs1333049 con- tributes to age-related disorder, conversely the absence of this allele might contribute to longevity. The identification of this genetic variant acting as a modulator of human lon- gevity may enlighten one aspect of the complex functional role of the 9p21.3 locus and may prompt further research into the role played by this chromosomal region not only in age-related disorders but also in aging control and modula- tion of life span. Intriguingly, proximal to rs1333049 lie two cyclin-dependent kinase inhibitor genes, CDKN2a and CDKN2b, which regulate the G phase of the cell cycle by 1 inhibition of cyclin-cyclin–dependent kinases.23 This raises the fascinating possibility that rs1333049 may modulate the rate of cellular aging.

Several limitations must be considered in the interpreta- tion of our findings. First, interpreting the results is limited by the relatively insufficient sample size. Therefore, the present findings need to be strengthened by increasing samples size and functional studies. A second limitation of our study is that we do not have a replication cohort for our findings. Unfortunately, it is very challenging to find repli- cation cohorts for studies in centenarians. However, the re- sults of the pilot study may stimulate further research in the role of 9p21.3 locus in aging and longevity. Finally, our in- vestigation was performed on a convenience sample of Caucasian subjects from Italy. Hence, replication of our findings in different populations is necessary.

Yao Y. A common variant on chromosome

p

affects the risk of early-onset coronary artery disease. Mol Biol Rep

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Shen GQ, Rao S, Martinelli N, Li L, Olivieri O, Corrocher R, Abdullah KG, Hazen SL, Smith J, Barnard J, Plow EF, Girelli D, Wang QK. Association between four SNPs on chromo- some

p

and myocardial infarction is replicated in an Italian population. J Hum Genet

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