title: Disease-associated polymorphisms in 9p21 are not associated with extreme longevity.
abstract: OBJECTIVE
  The 9p21 region has been pointed out by the genome-wide association studies as a hot spot for disease-associated variants. Most of the diseases linked with the locus are aging-related conditions, such us cardiovascular disease, diabetes and cancer. Centenarians are known to present a reduced risk and delayed onset for these conditions. Here, we aimed to assess if the 9p21 variants contribute to this protection by possibly altering basic aging mechanisms.
  
  
  METHODS
  We genotyped 15 tag single-nucleotide polymorphisms (SNP) along the CDKN2A/B/ANRIL locus in 1505 individuals. The participants were divided in three groups: centenarians, septuagenarians and young controls. Centenarians were 593 participants (age range 100-116 years, mean 105.9 years), septuagenarians were 434 volunteers aged between 69 and 71 years (mean 70.1 ± 0.9 years) and the 478 young controls were under the age of 50 years (range 14-50 years, mean 41.8 years). We genotyped the SNP rs1333049 in an additional sample of 231 coronary artery disease patients to confirm the 9p21 association.
  
  
  RESULTS
  The leading coronary artery disease-associated SNP rs1333049 was associated with coronary artery disease; however, none of the 9p21 SNP evaluated in the present study were associated with extreme longevity.
  
  
  CONCLUSIONS
  Our findings suggest that the 9p21 disease-associated polymorphisms do not contribute to the life-long protection from cardiovascular and other age-related diseases observed in centenarians. It is likely that this protection is mediated by mechanisms different from the ones underlying the 9p21 association.
authors.affiliation: Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Ada
authors.initials: A
authors.lastname: Congrains
authors.affiliation: Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Osaka, Japan.|Division of Health Sciences, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Kamide
authors.affiliation: Department of Geriatric Medicine, Keio University, Keio, Japan.
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Hirose
authors.affiliation: Department of Geriatric Medicine, Keio University, Keio, Japan.
authors.forename: Yasumichi
authors.initials: Y
authors.lastname: Arai
authors.affiliation: Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Ryousuke
authors.initials: R
authors.lastname: Oguro
authors.affiliation: Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Chikako
authors.initials: C
authors.lastname: Nakama
authors.affiliation: Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Imaizumi
authors.affiliation: Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kawai
authors.affiliation: Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kusunoki
authors.affiliation: Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Onishi-Takeya
authors.affiliation: Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Takeya
authors.affiliation: Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Sugimoto
authors.affiliation: Department of Second Internal Medicine, Sapporo Medical University, Sapporo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Akasaka
authors.affiliation: Department of Second Internal Medicine, Sapporo Medical University, Sapporo, Japan.
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Saitoh
authors.affiliation: Department of Second Internal Medicine, Sapporo Medical University, Sapporo, Japan.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Miura
authors.affiliation: Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Awata
authors.affiliation: Department of Gene Diagnosis and Therapeutics, Research Institute, National Center for Global health and Medicine, Tokyo, Japan.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Kato
authors.affiliation: Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Osaka, Japan.|Department of Clinical Gene Therapy, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Katsuya
authors.affiliation: Department of Prosthodontics and Oral Rehabilitation, Osaka University Graduate School of Dentistry, Osaka, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Ikebe
authors.affiliation: Department of Clinical Thanatology and Geriatric Behavioral Science, Graduate School of Human Sciences, Osaka University, Osaka, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Gondo
authors.affiliation: Department of Geriatric Medicine and Nephrology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Rakugi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D003324:Coronary Artery Disease / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D015810:Linkage Disequilibrium; D008136:Longevity / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D055815:Young Adult
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D005819:Genetic Markers
keywords: aging; atherosclerosis; genetic predisposition; longevity; polymorphism