Evidence from case–control and longitudinal studies supports associations of genetic variation in APOE, CETP, and IL6 with human longevity
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- 作者：Mette Soerensen (1) (2) (3)
Serena Dato (1) (4)
Qihua Tan (1) (2) (3)
Mikael Thinggaard (1)
Rabea Kleindorp (5)
Marian Beekman (6) (7)
H. Eka D. Suchiman (6) (7)
Rune Jacobsen (1)
Matt McGue (1) (8)
Tinna Stevnsner (9)
Vilhelm A. Bohr (10) (9)
Anton J. M. de Craen (11)
Rudi G. J. Westendorp (11)
Stefan Schreiber (5)
P. Eline Slagboom (6) (7)
Almut Nebel (5)
James W. Vaupel (1) (12)
Kaare Christensen (1) (2) (3)
Lene Christiansen (1) (2) (3) - 关键词：Human longevity ; Candidate gene association study ; Case–control data ; Longitudinal data
- 刊名：AGE
- 出版年：2013
- 出版时间：April 2013
- 年：2013
- 卷：35
- 期：2
- 页码：487-500
- 全文大小：290KB
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75. Zajc PM, Skaric-Juric T, Smolej NN, Tomas Z, Krajacic P, Milicic J, Barbalic M, Tomek-Roksandic S (2012) Angiotensin-converting enzyme deletion allele is beneficial for the longevity of Europeans. Age (Dordr). doi:10.1007/s11357-011-9270-0 - 作者单位：Mette Soerensen (1) (2) (3)
Serena Dato (1) (4)
Qihua Tan (1) (2) (3)
Mikael Thinggaard (1)
Rabea Kleindorp (5)
Marian Beekman (6) (7)
H. Eka D. Suchiman (6) (7)
Rune Jacobsen (1)
Matt McGue (1) (8)
Tinna Stevnsner (9)
Vilhelm A. Bohr (10) (9)
Anton J. M. de Craen (11)
Rudi G. J. Westendorp (11)
Stefan Schreiber (5)
P. Eline Slagboom (6) (7)
Almut Nebel (5)
James W. Vaupel (1) (12)
Kaare Christensen (1) (2) (3)
Lene Christiansen (1) (2) (3)
1. The Danish Aging Research Center, Epidemiology, Institute of Public Health, University of Southern Denmark, J.B. Winsloews Vej 9B, 5000, Odense C, Denmark
2. Department of Clinical Genetics, Odense University Hospital, Sdr. Boulevard 29, 5000, Odense C, Denmark
3. Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Sdr. Boulevard 29, 5000, Odense C, Denmark
4. Department of Cell Biology, University of Calabria, Ponte Pietro Bucci cubo 4C, 87036, Rende, Cosenza, Italy
5. Institute of Clinical Molecular Biology, University Hospital Schleswig-Holstein and Christian-Albrechts-University, Schittenhelmstrasse 12, 24105, Kiel, Germany
6. Department of Molecular Epidemiology, Leiden University Medical Center, S5-P, PO Box 9600, 2300 RC, Leiden, the Netherlands
7. Netherlands Consortium for Healthy Ageing, Leiden University Medical Center, 2300 RC, Leiden, the Netherlands
8. Department of Psychology, University of Minnesota, N218 Elliott Hall 75 East River Road, Minneapolis, MN, USA
9. The Danish Aging Research Center, Department of Molecular Biology, Aarhus University, C. F. Moellers Allé 3, 8000, Aarhus C, Denmark
10. Laboratory of Molecular Gerontology, National Institute on Aging, National Institute of Health, 5600 Nathan Shock Drive, Baltimore, MD, USA
11. Department of Gerontology and Geriatrics, Leiden University Medical Center, C2-R, PO Box 9600, 2300 RC, Leiden, the Netherlands
12. Max Planck Institute for Demographic Research, Konrad-Zuse-Str. 1, 18057, Rostock, Germany - ISSN：1574-4647
文摘
In this study, we investigated 102 single-nucleotide polymorphisms (SNPs) covering the common genetic variation in 16 genes recurrently regarded as candidates for human longevity: APOE; ACE; CETP; HFE; IL6; IL6R; MTHFR; TGFB1; APOA4; APOC3; SIRTs 1, 3, 6; and HSPAs 1A, 1L, 14. In a case–control study of 1,089 oldest-old (ages 92-3) and 736 middle-aged Danes, the minor allele frequency (MAF) of rs769449 (APOE) was significantly decreased in the oldest-old, while the MAF of rs9923854 (CETP) was significantly enriched. These effects were supported when investigating 1,613 oldest-old (ages 95-10) and 1,104 middle-aged Germans. rs769449 was in modest linkage equilibrium (R 2--.55) with rs429358 of the APOE-ε4 haplotype and adjusting for rs429358 eliminated the association of rs769449, indicating that the association likely reflects the well-known effect of rs429358. Gene-based analysis confirmed the effects of variation in APOE and CETP and furthermore pointed to HSPA14 as a longevity gene. In a longitudinal study with 11?years of follow-up on survival in the oldest-old Danes, only one SNP, rs2069827 (IL6), was borderline significantly associated with survival from age 92 (P-corrected--.064). This advantageous effect of the minor allele was supported when investigating a Dutch longitudinal cohort (N--63) of oldest-old (age 85+). Since rs2069827 was located in a putative transcription factor binding site, quantitative RNA expression studies were conducted. However, no difference in IL6 expression was observed between rs2069827 genotype groups. In conclusion, we here support and expand the evidence suggesting that genetic variation in APOE, CETP, and IL6, and possible HSPA14, is associated with human longevity.