Telomere length is associated with ACE I/D polymorphism in hypertensive patients with left ventricular hypertrophy

被引:7
作者
Fyhrquist, Frej [1 ,2 ]
Eriksson, Anders [1 ,3 ]
Saijonmaa, Outi [1 ,2 ]
Nordestgaard, Borge G. [4 ]
Kontula, Kimmo [2 ]
de Faire, Ulf [5 ]
Ibsen, Hans [6 ]
Kjeldsen, Sverre [7 ]
Os, Ingrid [8 ]
Dahlof, Bjorn [9 ]
机构
[1] Minerva Fdn, Helsinki, Finland
[2] Univ Helsinki, Cent Hosp, Dept Internal Med, FIN-00014 Helsinki, Finland
[3] Univ Helsinki, Fac Vet Med, Dept Equine & Small Anim Med, FIN-00014 Helsinki, Finland
[4] Univ Copenhagen, Dept Clin Biochem, DK-1168 Copenhagen, Denmark
[5] Karolinska Inst, Div Cardiovasc Epidemiol, S-10401 Stockholm, Sweden
[6] Holbaek Cent Hosp, Holbaek, Denmark
[7] Univ Michigan, Ann Arbor, MI 48109 USA
[8] Ullevaal Univ Hosp, Dept Nephrol, Ullevaal, Norway
[9] Sahlgrens Univ Hosp, Ostra, Sweden
关键词
Telomere length; ACE I/D polymorphism; hypertension; left ventricular hypertrophy; CONVERTING-ENZYME GENE; BLOOD-PRESSURE; INSERTION/DELETION POLYMORPHISM; CARDIOVASCULAR-DISEASE; OXIDATIVE STRESS; PULSE PRESSURE; ANGIOTENSIN; MORTALITY; RISK; MORBIDITY;
D O I
10.1177/1470320312460292
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
Introduction: Short telomeres are often associated with cardiovascular risk factors and age-related diseases, while the angiotensin converting enzyme (ACE) gene insertion/deletion polymorphism (DD, ID, II) has shown such associations less consistently. We hypothesized that telomere length and association of telomere length with cardiovascular risk is affected by ACE (I/D) genotype. Methods: We measured leucocyte telomere length (LTL) by Southern blot and analysed ACE I/D genotypes in 1249 subjects with hypertension and left ventricular hypertrophy (LVH). We examined interactions of ACE I/D genotype with LTL and cardiovascular risk. Results: Mean LTL in DD or ID genotype was shorter (8.15 and 8.14 kb, respectively), than in II genotype (8.27 kb, p=0.0005). This difference was significant in the younger subjects (55-64 years, p=0.02) but not in the older group (65-80 years, p=0.56 ). In DD but not I/D or II genotype, proportion of short telomeres (<5 kb) was related to Framingham risk score. Conclusions: Shorter LTL in genotypes DD or ID suggests a negative effect of the D allele on telomere length. Homozygocity for the D allele appears to strengthen the association of telomere length with increased cardiovascular risk in elderly hypertensive subjects with LVH.
引用
收藏
页码:227 / 234
页数:8
相关论文
共 43 条
[1]   ACE gene polymorphism in cardiovascular disease -: Meta-analyses of small and large studies in whites [J].
Agerholm-Larsen, B ;
Nordestgaard, BG ;
Tybjaerg-Hansen, A .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2000, 20 (02) :484-492
[2]   Pharmacogenetic association of the angiotensin-converting enzyme insertion/deletion polymorphism on blood pressure and cardiovascular risk in relation to antihypertensive treatment - The genetics of hypertension-associated treatment (GenHAT) study [J].
Arnett, DK ;
Davis, BR ;
Ford, CE ;
Boerwinkle, E ;
Leiendecker-Foster, C ;
Miller, MB ;
Black, H ;
Eckfeldt, JH .
CIRCULATION, 2005, 111 (25) :3374-3383
[3]   Impartial comparative analysis of measurement of leukocyte telomere length/DNA content by Southern blots and qPCR [J].
Aviv, Abraham ;
Hunt, Steven C. ;
Lin, Jue ;
Cao, Xiaojian ;
Kimura, Masayuki ;
Blackburn, Elizabeth .
NUCLEIC ACIDS RESEARCH, 2011, 39 (20)
[4]   The load of short telomeres, estimated by a new method, Universal STELA, correlates with number of senescent cells [J].
Bendix, Laila ;
Horn, Peer Bendix ;
Jensen, Uffe Birk ;
Rubelj, Ivica ;
Kolvraa, Steen .
AGING CELL, 2010, 9 (03) :383-397
[5]   Telomere length as an indicator of biological aging - The gender effect and relation with pulse pressure and pulse wave velocity [J].
Benetos, A ;
Okuda, K ;
Lajemi, M ;
Kimura, M ;
Thomas, F ;
Skurnick, J ;
Labat, C ;
Bean, K ;
Aviv, A .
HYPERTENSION, 2001, 37 (02) :381-385
[6]   Switching and signaling at the telomere [J].
Blackburn, EH .
CELL, 2001, 106 (06) :661-673
[7]   Telomeres and human disease: Ageing, cancer and beyond [J].
Blasco, MA .
NATURE REVIEWS GENETICS, 2005, 6 (08) :611-622
[8]   White cell telomere length and risk of premature myocardial infarction [J].
Brouilette, S ;
Singh, RK ;
Thompson, JR ;
Goodall, AH ;
Samani, NJ .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2003, 23 (05) :842-846
[9]   Association between telomere length in blood and mortality in people aged 60 years or older [J].
Cawthon, RM ;
Smith, KR ;
O'Brien, E ;
Sivatchenko, A ;
Kerber, RA .
LANCET, 2003, 361 (9355) :393-395
[10]   The effects of social status on biological aging as measured by white-blood-cell telomere length [J].
Cherkas, L. F. ;
Aviv, A. ;
Valdes, A. M. ;
Hunkin, J. L. ;
Gardner, J. P. ;
Surdulescu, G. L. ;
Kimura, M. ;
Spector, T. D. .
AGING CELL, 2006, 5 (05) :361-365