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AGE

, Volume 36, Issue 2, pp 933–943 | Cite as

The rs1333049 polymorphism on locus 9p21.3 and extreme longevity in Spanish and Japanese cohorts

  • Tomàs Pinós
  • Noriyuki Fuku
  • Yolanda Cámara
  • Yasumichi Arai
  • Yukiko Abe
  • Gabriel Rodríguez-Romo
  • Nuria Garatachea
  • Alejandro Santos-Lozano
  • Elisabet Miro-Casas
  • Marisol Ruiz-Meana
  • Imanol Otaegui
  • Haruka Murakami
  • Motohiko Miyachi
  • David Garcia-Dorado
  • Kunihiko Hinohara
  • Antoni L. Andreu
  • Akinori Kimura
  • Nobuyoshi Hirose
  • Alejandro Lucia
Article

Abstract

The rs1333049 (G/C) polymorphism located on chromosome 9p21.3 is a candidate to influence extreme longevity owing to its association with age-related diseases, notably coronary artery disease (CAD). We compared allele/genotype distributions of rs1333049 in cases (centenarians) and controls (younger adults, without (healthy) or with CAD) in two independent cohorts: Spanish (centenarians: n = 152, 128 women, 100–111 years; healthy controls: n = 343, 212 women, age <50 years; CAD controls: n = 98, 32 women, age ≤65 years) and Japanese (centenarians: n = 742, 623 women, 100–115 years; healthy controls: n = 920, 511 women, < 60 years; CAD controls: n = 395, 45 women, age ≤65 years). The frequency of the “risk” C-allele tended to be lower in Spanish centenarians (47.0 %) than in their healthy (52.9 %, P = 0.088) or CAD controls (55.1 %, P = 0.078), and significant differences were found in genotype distributions (P = 0.034 and P = 0.045), with a higher frequency of the GG genotype in cases than in both healthy and CAD controls as well as a lower proportion of the CG genotype compared with healthy controls. In the Japanese cohort, the main finding was that the frequency of the C-allele did not differ between centenarians (46.4 %) and healthy controls (47.3 %, P = 0.602), but it was significantly lower in the former than in CAD controls (57.2 %, P < 0.001). Although more research is needed, the present and recent pioneer findings (Rejuvenation Res 13:23–26, 2010) suggest that the rs1333049 polymorphism could be among the genetic contributors to exceptional longevity in Southern European populations, albeit this association does not exist in the healthy (CAD-free) Japanese population.

Keywords

Centenarians Genetics Coronary artery disease CDKN2A CDKN2B 

Notes

Acknowledgments

This study was funded by the Fondo de Investigaciones Sanitarias (FIS, refs. # PI12/00914, PI10/00036, and PI12/00788) and was supported in part by grants from the program “A Grant-in-Aid for Challenging Exploratory Research” (24650414 to N. Fuku) from the Ministry of Education, Culture, Sports, Science and Technology and by a Grant-in-Aid for Scientific Research from the Ministry of Health, Labor, and Welfare of Japan (to M. Miyachi).

References

  1. Angelakopoulou A, Shah T, Sofat R, Shah S, Berry DJ, Cooper J, Palmen J, Tzoulaki I, Wong A, Jefferis BJ, Maniatis N, Drenos F, Gigante B, Hardy R, Laxton RC, Leander K, Motterle A, Simpson IA, Smeeth L, Thomson A, Verzilli C, Kuh D, Ireland H, Deanfield J, Caulfield M, Wallace C, Samani N, Munroe PB, Lathrop M, Fowkes FG, Marmot M, Whincup PH, Whittaker JC, de Faire U, Kivimaki M, Kumari M, Hypponen E, Power C, Humphries SE, Talmud PJ, Price J, Morris RW, Ye S, Casas JP, Hingorani AD (2012) Comparative analysis of genome-wide association studies signals for lipids, diabetes, and coronary heart disease: Cardiovascular Biomarker Genetics Collaboration. Eur Heart J 33(3):393–407. doi: 10.1093/eurheartj/ehr225 PubMedCentralPubMedCrossRefGoogle Scholar
  2. Arlestig L, Rantapaa-Dahlqvist S (2012) Polymorphisms of the genes encoding CD40 and growth differentiation factor 15 and in the 9p21.3 region in patients with rheumatoid arthritis and cardiovascular disease. J Rheumatol 39(5):939–945. doi: 10.3899/jrheum.111336 PubMedCrossRefGoogle Scholar
  3. Biros E, Cooper M, Palmer LJ, Walker PJ, Norman PE, Golledge J (2010) Association of an allele on chromosome 9 and abdominal aortic aneurysm. Atherosclerosis 212(2):539–542. doi: 10.1016/j.atherosclerosis.2010.06.015 PubMedCentralPubMedCrossRefGoogle Scholar
  4. Bown MJ, Braund PS, Thompson J, London NJ, Samani NJ, Sayers RD (2008) Association between the coronary artery disease risk locus on chromosome 9p21.3 and abdominal aortic aneurysm. Circ Cardiovasc Genet 1(1):39–42. doi: 10.1161/CIRCGENETICS.108.789727 PubMedCrossRefGoogle Scholar
  5. Bressler J, Folsom AR, Couper DJ, Volcik KA, Boerwinkle E (2010) Genetic variants identified in a European genome-wide association study that were found to predict incident coronary heart disease in the Atherosclerosis Risk in Communities Study. Am J Epidemiol 171(1):14–23. doi: 10.1093/aje/kwp377 PubMedCentralPubMedCrossRefGoogle Scholar
  6. Buysschaert I, Carruthers KF, Dunbar DR, Peuteman G, Rietzschel E, Belmans A, Hedley A, De Meyer T, Budaj A, Van de Werf F, Lambrechts D, Fox KA (2010) A variant at chromosome 9p21 is associated with recurrent myocardial infarction and cardiac death after acute coronary syndrome: the GRACE Genetics Study. Eur Heart J 31(9):1132–1141. doi: 10.1093/eurheartj/ehq053 PubMedCentralPubMedCrossRefGoogle Scholar
  7. Christensen K, McGue M, Petersen I, Jeune B, Vaupel JW (2008) Exceptional longevity does not result in excessive levels of disability. Proc Natl Acad Sci U S A 105(36):13274–13279. doi: 10.1073/pnas.0804931105 PubMedCentralPubMedCrossRefGoogle Scholar
  8. Cluett C, McDermott MM, Guralnik J, Ferrucci L, Bandinelli S, Miljkovic I, Zmuda JM, Li R, Tranah G, Harris T, Rice N, Henley W, Frayling TM, Murray A, Melzer D (2009) The 9p21 myocardial infarction risk allele increases risk of peripheral artery disease in older people. Circ Cardiovasc Genet 2(4):347–353. doi: 10.1161/CIRCGENETICS.108.825935 PubMedCentralPubMedCrossRefGoogle Scholar
  9. Dandona S, Stewart AF, Chen L, Williams K, So D, O’Brien E, Glover C, Lemay M, Assogba O, Vo L, Wang YQ, Labinaz M, Wells GA, McPherson R, Roberts R (2010) Gene dosage of the common variant 9p21 predicts severity of coronary artery disease. J Am Coll Cardiol 56(6):479–486. doi: 10.1016/j.jacc.2009.10.092 PubMedCrossRefGoogle Scholar
  10. Dutta A, Henley W, Lang IA, Murray A, Guralnik J, Wallace RB, Melzer D (2011) The coronary artery disease-associated 9p21 variant and later life 20-year survival to cohort extinction. Circ Cardiovasc Genet 4(5):542–548. doi: 10.1161/CIRCGENETICS.111.960146 PubMedCrossRefGoogle Scholar
  11. Ellis KL, Pilbrow AP, Frampton CM, Doughty RN, Whalley GA, Ellis CJ, Palmer BR, Skelton L, Yandle TG, Palmer SC, Troughton RW, Richards AM, Cameron VA (2010) A common variant at chromosome 9P21.3 is associated with age of onset of coronary disease but not subsequent mortality. Circ Cardiovasc Genet 3(3):286–293. doi: 10.1161/CIRCGENETICS.109.917443 PubMedCrossRefGoogle Scholar
  12. Emanuele E, Fontana JM, Minoretti P, Geroldi D (2010) Preliminary evidence of a genetic association between chromosome 9p21.3 and human longevity. Rejuvenation Res 13(1):23–26. doi: 10.1089/rej.2009.0970 PubMedCrossRefGoogle Scholar
  13. Emanuele E, Lista S, Ghidoni R, Binetti G, Cereda C, Benussi L, Maletta R, Bruni AC, Politi P (2011) Chromosome 9p21.3 genotype is associated with vascular dementia and Alzheimer’s disease. Neurobiol Aging 32(7):1231–1235. doi: 10.1016/j.neurobiolaging.2009.07.003 PubMedCrossRefGoogle Scholar
  14. Farzaneh-Far R, Na B, Schiller NB, Whooley MA (2009) Lack of association of chromosome 9p21.3 genotype with cardiovascular structure and function in persons with stable coronary artery disease: the Heart and Soul Study. Atherosclerosis 205(2):492–496. doi: 10.1016/j.atherosclerosis.2008.12.026 PubMedCentralPubMedCrossRefGoogle Scholar
  15. Gondo Y, Hirose N, Arai Y, Inagaki H, Masui Y, Yamamura K, Shimizu K, Takayama M, Ebihara Y, Nakazawa S, Kitagawa K (2006) Functional status of centenarians in Tokyo, Japan: developing better phenotypes of exceptional longevity. J Gerontol A Biol Sci Med Sci 61(3):305–310PubMedCrossRefGoogle Scholar
  16. Helgadottir A, Thorleifsson G, Manolescu A, Gretarsdottir S, Blondal T, 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 (2007) A common variant on chromosome 9p21 affects the risk of myocardial infarction. Science 316(5830):1491–1493. doi: 10.1126/science.1142842 PubMedCrossRefGoogle Scholar
  17. 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, 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 (2008) The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm. Nat Genet 40(2):217–224. doi: 10.1038/ng.72 PubMedCrossRefGoogle Scholar
  18. Hinohara K, Nakajima T, Takahashi M, Hohda S, Sasaoka T, Nakahara K, Chida K, Sawabe M, Arimura T, Sato A, Lee BS, Ban JM, Yasunami M, Park JE, Izumi T, Kimura A (2008) Replication of the association between a chromosome 9p21 polymorphism and coronary artery disease in Japanese and Korean populations. J Hum Genet 53(4):357–359PubMedCrossRefGoogle Scholar
  19. Hiura Y, Fukushima Y, Yuno M, Sawamura H, Kokubo Y, Okamura T, Tomoike H, Goto Y, Nonogi H, Takahashi R, Iwai N (2008) Validation of the association of genetic variants on chromosome 9p21 and 1q41 with myocardial infarction in a Japanese population. Circ J 72(8):1213–1217PubMedCrossRefGoogle Scholar
  20. 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 (2009) The impact of newly identified loci on coronary heart disease, stroke and total mortality in the MORGAM prospective cohorts. Genet Epidemiol 33(3):237–246. doi: 10.1002/gepi.20374 PubMedCentralPubMedCrossRefGoogle Scholar
  21. Koch W, Turk S, Erl A, Hoppmann P, Pfeufer A, King L, Schomig A, Kastrati A (2011) The chromosome 9p21 region and myocardial infarction in a European population. Atherosclerosis 217(1):220–226. doi: 10.1016/j.atherosclerosis.2011.03.014 PubMedCrossRefGoogle Scholar
  22. Maitra A, Dash D, John S, Sannappa PR, Das AP, Shanker J, Rao VS, Sridhara H, Kakkar VV (2009) A common variant in chromosome 9p21 associated with coronary artery disease in Asian Indians. J Genet 88(1):113–118PubMedCrossRefGoogle Scholar
  23. McPherson R (2010) Chromosome 9p21 and coronary artery disease. N Engl J Med 362(18):1736–1737. doi: 10.1056/NEJMcibr1002359 PubMedCrossRefGoogle Scholar
  24. Mendonca I, dos Reis RP, Pereira A, Cafe H, Serrao M, Sousa AC, Freitas AI, Guerra G, Freitas S, Freitas C, Ornelas I, Brehm A, Araujo JJ (2011) Independent association of the variant rs1333049 at the 9p21 locus and coronary heart disease. Rev Port Cardiol 30(6):575–591PubMedGoogle Scholar
  25. Minoretti P, Gazzaruso C, Vito CD, Emanuele E, Bianchi M, Coen E, Reino M, Geroldi D (2006) Effect of the functional toll-like receptor 4 Asp299Gly polymorphism on susceptibility to late-onset Alzheimer’s disease. Neurosci Lett 391(3):147–149. doi: 10.1016/j.neulet.2005.08.047 PubMedCrossRefGoogle Scholar
  26. Muendlein A, Saely CH, Rhomberg S, Sonderegger G, Loacker S, Rein P, Beer S, Vonbank A, Winder T, Drexel H (2009) Evaluation of the association of genetic variants on the chromosomal loci 9p21.3, 6q25.1, and 2q36.3 with angiographically characterized coronary artery disease. Atherosclerosis 205(1):174–180. doi: 10.1016/j.atherosclerosis.2008.10.035 PubMedCrossRefGoogle Scholar
  27. O’Donnell CJ, Kavousi M, Smith AV, Kardia SL, Feitosa MF, Hwang SJ, Sun YV, Province MA, Aspelund T, Dehghan A, Hoffmann U, Bielak LF, Zhang Q, Eiriksdottir G, van Duijn CM, Fox CS, de Andrade M, Kraja AT, Sigurdsson S, Elias-Smale SE, Murabito JM, Launer LJ, van der Lugt A, Kathiresan S, Krestin GP, Herrington DM, Howard TD, Liu Y, Post W, Mitchell BD, O’Connell JR, Shen H, Shuldiner AR, Altshuler D, Elosua R, Salomaa V, Schwartz SM, Siscovick DS, Voight BF, Bis JC, Glazer NL, Psaty BM, Boerwinkle E, Heiss G, Blankenberg S, Zeller T, Wild PS, Schnabel RB, Schillert A, Ziegler A, Munzel TF, White CC, Rotter JI, Nalls M, Oudkerk M, Johnson AD, Newman AB, Uitterlinden AG, Massaro JM, Cunningham J, Harris TB, Hofman A, Peyser PA, Borecki IB, Cupples LA, Gudnason V, Witteman JC (2011) Genome-wide association study for coronary artery calcification with follow-up in myocardial infarction. Circulation 124(25):2855–2864. doi: 10.1161/CIRCULATIONAHA.110.974899 PubMedCentralPubMedCrossRefGoogle Scholar
  28. Palomaki GE, Melillo S, Bradley LA (2010) Association between 9p21 genomic markers and heart disease: a meta-analysis. JAMA 303(7):648–656. doi: 10.1001/jama.2010.118 PubMedCrossRefGoogle Scholar
  29. Peng WH, Lu L, Zhang Q, Zhang RY, Wang LJ, Yan XX, Chen QJ, Shen WF (2009) Chromosome 9p21 polymorphism is associated with myocardial infarction but not with clinical outcome in Han Chinese. Clin Chem Lab Med 47(8):917–922. doi: 10.1515/CCLM.2009.215 PubMedCrossRefGoogle Scholar
  30. Plichart M, Empana JP, Lambert JC, Amouyel P, Tiret L, Letenneur L, Berr C, Tzourio C, Ducimetiere P (2012) Single polymorphism nucleotide rs1333049 on chromosome 9p21 is associated with carotid plaques but not with common carotid intima-media thickness in older adults. A combined analysis of the Three-City and the EVA studies. Atherosclerosis 222(1):187–190. doi: 10.1016/j.atherosclerosis.2012.02.038 PubMedCrossRefGoogle Scholar
  31. Ruiz JR, Fiuza-Luces C, Buxens A, Cano-Nieto A, Gomez-Gallego F, Santiago C, Rodriguez-Romo G, Garatachea N, Lao JI, Moran M, Lucia A (2012) Are centenarians genetically predisposed to lower disease risk? Age 34(5):1269–1283. doi: 10.1007/s11357-011-9296-3 PubMedCentralPubMedCrossRefGoogle Scholar
  32. Saleheen D, Alexander M, Rasheed A, Wormser D, Soranzo N, Hammond N, Butterworth A, Zaidi M, Haycock P, Bumpstead S, Potter S, Blackburn H, Gray E, Di Angelantonio E, Kaptoge S, Shah N, Samuel M, Janjua A, Sheikh N, Haider SR, Murtaza M, Ahmad U, Hakeem A, Memon MA, Mallick NH, Azhar M, Samad A, Rasheed SZ, Gardezi AR, Memon NA, Ghaffar A, Memon FU, Zaman KS, Kundi A, Yaqoob Z, Cheema LA, Qamar N, Faruqui A, Jooma R, Niazi JH, Hussain M, Kumar K, Saleem A, Daood MS, Memon F, Gul AA, Abbas S, Zafar J, Shahid F, Memon Z, Bhatti SM, Kayani W, Ali SS, Fahim M, Ishaq M, Frossard P, Deloukas P, Danesh J (2010) Association of the 9p21.3 locus with risk of first-ever myocardial infarction in Pakistanis: case–control study in South Asia and updated meta-analysis of Europeans. Arterioscler Thromb Vasc Biol 30(7):1467–1473. doi: 10.1161/ATVBAHA.109.197210 PubMedCrossRefGoogle Scholar
  33. Samani NJ, Erdmann J, Hall AS, Hengstenberg C, Mangino M, Mayer B, Dixon RJ, Meitinger T, Braund P, Wichmann HE, Barrett JH, Konig IR, Stevens SE, Szymczak S, Tregouet DA, Iles MM, Pahlke F, Pollard H, Lieb W, Cambien F, Fischer M, Ouwehand W, Blankenberg S, Balmforth AJ, Baessler A, Ball SG, Strom TM, Braenne I, Gieger C, Deloukas P, Tobin MD, Ziegler A, Thompson JR, Schunkert H (2007) Genomewide association analysis of coronary artery disease. N Engl J Med 357(5):443–453. doi: 10.1056/NEJMoa072366 PubMedCentralPubMedCrossRefGoogle Scholar
  34. Samani NJ, Deloukas P, Erdmann J, Hengstenberg C, Kuulasmaa K, McGinnis R, Schunkert H, Soranzo N, Thompson J, Tiret L, Ziegler A (2009) Large scale association analysis of novel genetic loci for coronary artery disease. Arterioscler Thromb Vasc Biol 29(5):774–780. doi: 10.1161/ATVBAHA.108.181388 PubMedCrossRefGoogle Scholar
  35. Saxena R, Voight BF, Lyssenko V, Burtt NP, de Bakker PI, Chen H, Roix JJ, Kathiresan S, Hirschhorn JN, Daly MJ, Hughes TE, Groop L, Altshuler D, Almgren P, Florez JC, Meyer J, Ardlie K, Bengtsson Bostrom K, Isomaa B, Lettre G, Lindblad U, Lyon HN, Melander O, Newton-Cheh C, Nilsson P, Orho-Melander M, Rastam L, Speliotes EK, Taskinen MR, Tuomi T, Guiducci C, Berglund A, Carlson J, Gianniny L, Hackett R, Hall L, Holmkvist J, Laurila E, Sjogren M, Sterner M, Surti A, Svensson M, Tewhey R, Blumenstiel B, Parkin M, Defelice M, Barry R, Brodeur W, Camarata J, Chia N, Fava M, Gibbons J, Handsaker B, Healy C, Nguyen K, Gates C, Sougnez C, Gage D, Nizzari M, Gabriel SB, Chirn GW, Ma Q, Parikh H, Richardson D, Ricke D, Purcell S (2007) Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science 316(5829):1331–1336. doi: 10.1126/science.1142358 PubMedCrossRefGoogle Scholar
  36. Scheffold T, Kullmann S, Huge A, Binner P, Ochs HR, Schols W, Thale J, Motz W, Hegge FJ, Stellbrink C, Dorsel T, Gulker H, Heuer H, Dinh W, Stoll M, Haltern G (2011) Six sequence variants on chromosome 9p21.3 are associated with a positive family history of myocardial infarction: a multicenter registry. BMC Cardiovasc Disord 11:9PubMedCentralPubMedCrossRefGoogle Scholar
  37. Schunkert H, Gotz A, Braund P, McGinnis R, Tregouet DA, Mangino M, Linsel-Nitschke P, Cambien F, Hengstenberg C, Stark K, Blankenberg S, Tiret L, Ducimetiere P, Keniry A, Ghori MJ, Schreiber S, El Mokhtari NE, Hall AS, Dixon RJ, Goodall AH, Liptau H, Pollard H, Schwarz DF, Hothorn LA, Wichmann HE, Konig IR, Fischer M, Meisinger C, Ouwehand W, Deloukas P, Thompson JR, Erdmann J, Ziegler A, Samani NJ (2008) Repeated replication and a prospective meta-analysis of the association between chromosome 9p21.3 and coronary artery disease. Circulation 117(13):1675–1684. doi: 10.1161/CIRCULATIONAHA.107.730614 PubMedCentralPubMedCrossRefGoogle Scholar
  38. Sebastiani P, Solovieff N, Dewan AT, Walsh KM, Puca A, Hartley SW, Melista E, Andersen S, Dworkis DA, Wilk JB, Myers RH, Steinberg MH, Montano M, Baldwin CT, Hoh J, Perls TT (2012) Genetic signatures of exceptional longevity in humans. PLoS One 7(1):e29848. doi: 10.1371/journal.pone.0029848 PubMedCentralPubMedCrossRefGoogle Scholar
  39. Shen GQ, Li L, Rao S, Abdullah KG, Ban JM, Lee BS, Park JE, Wang QK (2008a) Four SNPs on chromosome 9p21 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 28(2):360–365. doi: 10.1161/ATVBAHA.107.157248 PubMedCrossRefGoogle Scholar
  40. 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 (2008b) Association between four SNPs on chromosome 9p21 and myocardial infarction is replicated in an Italian population. J Hum Genet 53(2):144–150. doi: 10.1007/s10038-007-0230-6 PubMedCrossRefGoogle Scholar
  41. Smith JG, Melander O, Lovkvist H, Hedblad B, Engstrom G, Nilsson P, Carlson J, Berglund G, Norrving B, Lindgren A (2009) Common genetic variants on chromosome 9p21 confers risk of ischemic stroke: a large-scale genetic association study. Circ Cardiovasc Genet 2(2):159–164. doi: 10.1161/CIRCGENETICS.108.835173 PubMedCrossRefGoogle Scholar
  42. Takayama M, Hirose N, Arai Y, Gondo Y, Shimizu K, Ebihara Y, Yamamura K, Nakazawa S, Inagaki H, Masui Y, Kitagawa K (2007) Morbidity of Tokyo-area centenarians and its relationship to functional status. J Gerontol A Biol Sci Med Sci 62(7):774–782PubMedCrossRefGoogle Scholar
  43. Wang W, Peng W, Zhang X, Lu L, Zhang R, Zhang Q, Wang L, Chen Q, Shen W (2010) Chromosome 9p21.3 polymorphism in a Chinese Han population is associated with angiographic coronary plaque progression in non-diabetic but not in type 2 diabetic patients. Cardiovasc Diabetol 9:33PubMedCentralPubMedCrossRefGoogle Scholar
  44. Wellcome Trust Case Control Consortium (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447(7145):661–678. doi: 10.1038/nature05911 CrossRefGoogle Scholar
  45. Ye S, Willeit J, Kronenberg F, Xu Q, Kiechl S (2008) Association of genetic variation on chromosome 9p21 with susceptibility and progression of atherosclerosis: a population-based, prospective study. J Am Coll Cardiol 52(5):378–384. doi: 10.1016/j.jacc.2007.11.087 PubMedCrossRefGoogle Scholar
  46. Yu JT, Yu Y, Zhang W, Wu ZC, Li Y, Zhang N, Tan L (2010) Single nucleotide polymorphism rs1333049 on chromosome 9p21.3 is associated with Alzheimer’s disease in Han Chinese. Clin Chim Acta 411(17–18):1204–1207. doi: 10.1016/j.cca.2010.04.023 PubMedCrossRefGoogle Scholar

Copyright information

© American Aging Association 2013

Authors and Affiliations

  • Tomàs Pinós
    • 1
    • 11
  • Noriyuki Fuku
    • 2
  • Yolanda Cámara
    • 1
    • 11
  • Yasumichi Arai
    • 3
  • Yukiko Abe
    • 3
  • Gabriel Rodríguez-Romo
    • 4
  • Nuria Garatachea
    • 5
  • Alejandro Santos-Lozano
    • 6
  • Elisabet Miro-Casas
    • 7
  • Marisol Ruiz-Meana
    • 7
  • Imanol Otaegui
    • 7
  • Haruka Murakami
    • 8
  • Motohiko Miyachi
    • 8
  • David Garcia-Dorado
    • 7
  • Kunihiko Hinohara
    • 9
  • Antoni L. Andreu
    • 1
    • 11
  • Akinori Kimura
    • 9
  • Nobuyoshi Hirose
    • 3
  • Alejandro Lucia
    • 10
  1. 1.Departament de Patología Mitocondrial i NeuromuscularInstitut de Recerca Hospital Universitari Vall d’HebronBarcelonaSpain
  2. 2.Department of Genomics for Longevity and HealthTokyo Metropolitan Institute of GerontologyTokyoJapan
  3. 3.Department of Internal MedicineKeio University School of MedicineTokyoJapan
  4. 4.INEFUniversidad PolitécnicaMadridSpain
  5. 5.Facultad de Ciencias de la Salud y del DeporteUniversidad de ZaragozaHuescaSpain
  6. 6.Departmento de Ciencias BiomédicasUniversidad de LeónLeónSpain
  7. 7.Departamento de CardiologíaHospital Universitari Vall d’HebronBarcelonaSpain
  8. 8.Department of Health Promotion and ExerciseNational Institute of Health and NutritionTokyoJapan
  9. 9.Department of Molecular Pathogenesis, Medical Research InstituteTokyo Medical and Dental UniversityTokyoJapan
  10. 10.Universidad Europea and Instituto de Investigación Sanitaria Hospital 12 de Octubre (i+12)MadridSpain
  11. 11.CIBER de Enfermedades Raras (CIBERER)BarcelonaSpain

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