Disease-associated polymorphisms in 9p21 are not associated with extreme longevity

Ada Congrains, Kei Kamide, Nobuyoshi Hirose, Yasumichi Arai, Ryousuke Oguro, Chikako Nakama, Yuki Imaizumi, Tatsuo Kawai, Hiroshi Kusunoki, Hiroko Yamamoto, Miyuki Onishi-Takeya, Yasushi Takeya, Koichi Yamamoto, Ken Sugimoto, Hiroshi Akasaka, Shigeyuki Saitoh, Tetsuji Miura, Nobuhisa Awata, Norihiro Kato, Tomohiro KatsuyaKazunori Ikebe, Yasuyuki Gondo, Hiromi Rakugi

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Aim: 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.

Original languageEnglish
Pages (from-to)797-803
Number of pages7
JournalGeriatrics and Gerontology International
Volume15
Issue number6
DOIs
Publication statusPublished - 2015 Jun 1

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Single Nucleotide Polymorphism
Disease
Coronary Artery Disease
Genome-Wide Association Study
Volunteers
Cardiovascular Diseases
chronic illness
Neoplasms
cancer
Group

Keywords

  • Aging
  • Atherosclerosis
  • Genetic predisposition
  • Longevity
  • Polymorphism

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Gerontology
  • Health(social science)

Cite this

Disease-associated polymorphisms in 9p21 are not associated with extreme longevity. / Congrains, Ada; Kamide, Kei; Hirose, Nobuyoshi; Arai, Yasumichi; Oguro, Ryousuke; Nakama, Chikako; Imaizumi, Yuki; Kawai, Tatsuo; Kusunoki, Hiroshi; Yamamoto, Hiroko; Onishi-Takeya, Miyuki; Takeya, Yasushi; Yamamoto, Koichi; Sugimoto, Ken; Akasaka, Hiroshi; Saitoh, Shigeyuki; Miura, Tetsuji; Awata, Nobuhisa; Kato, Norihiro; Katsuya, Tomohiro; Ikebe, Kazunori; Gondo, Yasuyuki; Rakugi, Hiromi.

In: Geriatrics and Gerontology International, Vol. 15, No. 6, 01.06.2015, p. 797-803.

Research output: Contribution to journalArticle

Congrains, A, Kamide, K, Hirose, N, Arai, Y, Oguro, R, Nakama, C, Imaizumi, Y, Kawai, T, Kusunoki, H, Yamamoto, H, Onishi-Takeya, M, Takeya, Y, Yamamoto, K, Sugimoto, K, Akasaka, H, Saitoh, S, Miura, T, Awata, N, Kato, N, Katsuya, T, Ikebe, K, Gondo, Y & Rakugi, H 2015, 'Disease-associated polymorphisms in 9p21 are not associated with extreme longevity', Geriatrics and Gerontology International, vol. 15, no. 6, pp. 797-803. https://doi.org/10.1111/ggi.12346
Congrains, Ada ; Kamide, Kei ; Hirose, Nobuyoshi ; Arai, Yasumichi ; Oguro, Ryousuke ; Nakama, Chikako ; Imaizumi, Yuki ; Kawai, Tatsuo ; Kusunoki, Hiroshi ; Yamamoto, Hiroko ; Onishi-Takeya, Miyuki ; Takeya, Yasushi ; Yamamoto, Koichi ; Sugimoto, Ken ; Akasaka, Hiroshi ; Saitoh, Shigeyuki ; Miura, Tetsuji ; Awata, Nobuhisa ; Kato, Norihiro ; Katsuya, Tomohiro ; Ikebe, Kazunori ; Gondo, Yasuyuki ; Rakugi, Hiromi. / Disease-associated polymorphisms in 9p21 are not associated with extreme longevity. In: Geriatrics and Gerontology International. 2015 ; Vol. 15, No. 6. pp. 797-803.
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T1 - Disease-associated polymorphisms in 9p21 are not associated with extreme longevity

AU - Congrains, Ada

AU - Kamide, Kei

AU - Hirose, Nobuyoshi

AU - Arai, Yasumichi

AU - Oguro, Ryousuke

AU - Nakama, Chikako

AU - Imaizumi, Yuki

AU - Kawai, Tatsuo

AU - Kusunoki, Hiroshi

AU - Yamamoto, Hiroko

AU - Onishi-Takeya, Miyuki

AU - Takeya, Yasushi

AU - Yamamoto, Koichi

AU - Sugimoto, Ken

AU - Akasaka, Hiroshi

AU - Saitoh, Shigeyuki

AU - Miura, Tetsuji

AU - Awata, Nobuhisa

AU - Kato, Norihiro

AU - Katsuya, Tomohiro

AU - Ikebe, Kazunori

AU - Gondo, Yasuyuki

AU - Rakugi, Hiromi

PY - 2015/6/1

Y1 - 2015/6/1

N2 - Aim: 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.

AB - Aim: 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.

KW - Aging

KW - Atherosclerosis

KW - Genetic predisposition

KW - Longevity

KW - Polymorphism

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