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 language | English |
|---|---|
| Pages (from-to) | 797-803 |
| Number of pages | 7 |
| Journal | Geriatrics and Gerontology International |
| Volume | 15 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 2015 Jun 1 |
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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 journal › Article
}
TY - JOUR
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
UR - http://www.scopus.com/inward/record.url?scp=84930065980&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84930065980&partnerID=8YFLogxK
U2 - 10.1111/ggi.12346
DO - 10.1111/ggi.12346
M3 - Article
C2 - 25257646
AN - SCOPUS:84930065980
VL - 15
SP - 797
EP - 803
JO - Geriatrics and Gerontology International
JF - Geriatrics and Gerontology International
SN - 1447-0594
IS - 6
ER -