Common variants in SIRT1 and human longevity in a Chinese population

被引：17

作者：

Lin, Rong ^{[1
]}

Yan, Dongjing ^{[2
]}

Zhang, Yunxia ^{[2
]}

Liao, Xiaoping ^{[3
]}

Gong, Gu ^{[1
]}

Hu, Junjie ^{[1
,4
]}

Fu, Yunxin ^{[5
,6
,7
]}

Cai, Wangwei ^{[2
]}

机构：

[1] Hainan Med Coll, Dept Biol, Haikou 571199, Hainan, Peoples R China

[2] Hainan Med Coll, Dept Biochem & Mol Biol, Haikou 571199, Hainan, Peoples R China

[3] Hainan Med Coll, Affiliated Hosp, Dept Neurol, Haikou 571199, Hainan, Peoples R China

[4] Hainan Univ, Coll Agr, Haikou 570228, Hainan, Peoples R China

[5] Univ Texas Hlth Sci Ctr Houston, Div Biostat, 1200 Herman Pressler, Houston, TX 77025 USA

[6] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, 1200 Herman Pressler, Houston, TX 77025 USA

[7] Yunnan Univ, Lab Conservat & Utilizat Bioresources, Kunming 650091, Yunnan, Peoples R China

来源：

BMC MEDICAL GENETICS | 2016年 / 17卷

基金：

中国国家自然科学基金;

关键词：

SIRT1; Case-control association design; Human longevity; Single nucleotide polymorphism; GENOME-WIDE ASSOCIATION; PANCREATIC BETA-CELLS; TRANSCRIPTION FACTORS; CALORIE RESTRICTION; SIR2-LIKE PROTEINS; INSULIN-SECRETION; INCREASED DOSAGE; SURVIVAL; GENE; NAD;

D O I：

10.1186/s12881-016-0293-3

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Background: The silent information regulator SIR2/SIRT1gene has been demonstrated as regulating lifespan in many model organisms, including yeast, worms, fruit flies and rodents. SIRT1, the human homolog of SIR2, is considered a candidate gene as a modifier of human life expectancy. Methods: In the current study we included 616 long-lived individuals and 846 matched younger controls to investigate associations between 8 common single nucleotide polymorphisms (SNPs) (i.e., rs12778366, rs3758391, rs3740051, rs33957861, rs7896005, rs12413112, rs11599176 and rs4746720) in the SIRT1 gene and human longevity. Results: The 8 SNPs had strong linkage disequilibrium (LD) and were in an LD block, which was characterized by 4 common haplotypes that capture 99.3 % of the genetic variation present within it. We found no evidence for statistically significant associations between the tested SIRT1 SNPs and longevity at the allele, genotype or haplotype levels. Conclusions: Current findings show that several common variants in SIRT1 are not associated with human longevity.

引用

页数：7

共 34 条

[1] Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal degeneration [J].

Araki, T ;

Sasaki, Y ;

Milbrandt, J .

SCIENCE, 2004, 305 (5686) :1010-1013

[2] Extended longevity in mice lacking the insulin receptor in adipose tissue [J].

Blüher, M ;

Kahn, BB ;

Kahn, CR .

SCIENCE, 2003, 299 (5606) :572-574

[3] Sirt1 regulates insulin secretion by repressing UCP2 in pancreatic β cells [J].

Bordone, L ;

Motta, MC ;

Picard, F ;

Robinson, A ;

Jhala, US ;

Apfeld, J ;

McDonagh, T ;

Lemieux, M ;

McBurney, M ;

Szilvasi, A ;

Easlon, EJ ;

Lin, SJ ;

Guarente, L .

PLOS BIOLOGY, 2006, 4 (02) :210-220

[4] Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase [J].

Brunet, A ;

Sweeney, LB ;

Sturgill, JF ;

Chua, KF ;

Greer, PL ;

Lin, YX ;

Tran, H ;

Ross, SE ;

Mostoslavsky, R ;

Cohen, HY ;

Hu, LS ;

Cheng, HL ;

Jedrychowski, MP ;

Gygi, SP ;

Sinclair, DA ;

Alt, FW ;

Greenberg, ME .

SCIENCE, 2004, 303 (5666) :2011-2015

[5] A comparison of cataloged variation between International HapMap Consortium and 1000 Genomes Project data [J].

Buchanan, Carrie C. ;

Torstenson, Eric S. ;

Bush, William S. ;

Ritchie, Marylyn D. .

JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION, 2012, 19 (02) :289-294

[6] Genome-wide association study validation identifies novel loci for atherosclerotic cardiovascular disease [J].

Chen, X. ;

Li, S. ;

Yang, Y. ;

Yang, X. ;

Liu, Y. ;

Hu, W. ;

Jin, L. ;

Wang, X. .

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, 2012, 10 (08) :1508-1514

[7] Genome-wide association meta-analysis of human longevity identifies a novel locus conferring survival beyond 90 years of age [J].

Deelen, Joris ;

Beekman, Marian ;

Uh, Hae-Won ;

Broer, Linda ;

Ayers, Kristin L. ;

Tan, Qihua ;

Kamatani, Yoichiro ;

Bennet, Anna M. ;

Tamm, Riin ;

Trompet, Stella ;

Guobjartsson, Daniel F. ;

Flachsbart, Friederike ;

Rose, Giuseppina ;

Viktorin, Alexander ;

Fischer, Krista ;

Nygaard, Marianne ;

Cordell, Heather J. ;

Crocco, Paolina ;

Van den Akker, Erik B. ;

Bohringer, Stefan ;

Helmer, Quinta ;

Nelson, Christopher P. ;

Saunders, Gary I. ;

Alver, Maris ;

Andersen-Ranberg, Karen ;

Breen, Marie E. ;

van der Breggen, Ruud ;

Caliebe, Amke ;

Capri, Miriam ;

Cevenini, Elisa ;

Collerton, Joanna C. ;

Dato, Serena ;

Davies, Karen ;

Ford, Ian ;

Gampe, Jutta ;

Garagnani, Paolo ;

de Geus, Eco J. C. ;

Harrow, Jennifer ;

van Heemst, Diana ;

Heijmans, Bastiaan T. ;

Heinsen, Femke-Anouska ;

Hottenga, Jouke-Jan ;

Hofman, Albert ;

Jeune, Bernard ;

Jonsson, Palmi V. ;

Lathrop, Mark ;

Lechner, Doris ;

Martin-Ruiz, Carmen ;

Mcnerlan, Susan E. ;

Mihailov, Evelin .

HUMAN MOLECULAR GENETICS, 2014, 23 (16) :4420-4432

[8] Genome-wide association study identifies a single major locus contributing to survival into old age; the APOE locus revisited [J].

Deelen, Joris ;

Beekman, Marian ;

Uh, Hae-Won ;

Helmer, Quinta ;

Kuningas, Maris ;

Christiansen, Lene ;

Kremer, Dennis ;

van der Breggen, Ruud ;

Suchiman, H. Eka D. ;

Lakenberg, Nico ;

van den Akker, Erik B. ;

Passtoors, Willemijn M. ;

Tiemeier, Henning ;

van Heemst, Diana ;

de Craen, Anton J. ;

Rivadeneira, Fernando ;

de Geus, Eco J. ;

Perola, Markus ;

van der Ouderaa, Frans J. ;

Gunn, David A. ;

Boomsma, Dorret I. ;

Uitterlinden, Andre G. ;

Christensen, Kaare ;

van Duijn, Cornelia M. ;

Heijmans, Bastiaan T. ;

Houwing-Duistermaat, Jeanine J. ;

Westendorp, Rudi G. J. ;

Slagboom, P. Eline .

AGING CELL, 2011, 10 (04) :686-698

[9]

Fan X., 2013, POPUL J, V35, P14

[10] Sirtuin 1 (SIRT1) sequence variation is not associated with exceptional human longevity [J].

Flachsbart, F ;

Croucher, PJP ;

Nikolaus, S ;

Hampe, J ;

Cordes, C ;

Schreiber, S ;

Nebel, A .

EXPERIMENTAL GERONTOLOGY, 2006, 41 (01) :98-102

← 1 2 3 4 →