Genetic variants implicated in telomere length associated with left ventricular function in patients with hypertension and cardiac organ damage
Telomere length has emerged as a biological correlate for ageing, which in turn is a risk factor for the manifestation of cardiovascular diseases. This study investigated the relation between leucocyte telomere length (LTL) and its genetic background to cardiac structure and function in patients with arterial hypertension. We analysed a cohort of 1,106 treated hypertensive patients (83.3% males; mean age, 57.9 ± 9.8 years) with an ejection fraction (EF) over 40% and documented cardiovascular disease or target organ damage. LTL and genotypes of single nucleotide polymorphisms (SNPs), previously implicated in LTL, were determined by real-time PCR. The mean left ventricular mass index (LVMI) and EF were 51.8 ± 21.0 g/H2.7 and 61.1 ± 9.6%, respectively. In multivariate adjusted analysis, a 1.5-fold LTL was positively related with a 2.2% increase of LVMI (CI = 0.1% to 4.2%, p = 0.044) and an absolute increase in EF of 0.6% (CI = 0.1% to 1.1%, p = 0.028). One SNP near TERC (rs16847897) showed a significant absolute difference in EF dependent on allele status (rs16847897, G allele 2.7%; CI = 0.7% to 4.6%; praw = 0.008, pmt = 0.048, after adjustment for multiple testing). This applied also for two SNPs in BICD1 (rs2630578, C allele −1.8%; CI = −2.8% to −0.7%; praw = 0.002, pmt = 0.018; rs1151026, G allele −1.9%, CI = −3.0% to −0.8%; praw < 0.001, pmt = 0.002) with the extension that a frequent haplotype in BICD1 showed an absolute −1.8% (CI = −3.0% to −0.7%; praw = 0.002, pmt = 0.008) lower EF compared with those lacking this haplotype. Our results point to a role of genetic variants recently implicated in LTL for left ventricular function in hypertensive patients.
KeywordsAgeing Cardiac output Echocardiography Genetics Hypertension Clinical research Heart
We are grateful to all physicians, nurses and patients from the participating centres (listed in the Appendix online). We are particularly grateful to H. Buhlert and K. Stolze who were responsible for central data management and to K. Kossatz for excellent technical assistance. This work was supported by a grant from the Bundesministerium für Bildung und Forschung, Nationales Genomforschungsnetz, Herzkreislaufnetz in NGFNplus (grant number 01GS0839), Germany.
Conflicts of interest
The authors declare no conflicts of interest.
- 5.Brouilette SW, Moore JS, McMahon AD, Thompson JR, Ford I, Shepherd J, Packard CJ, Samani NJ (2007) Telomere length, risk of coronary heart disease, and statin treatment in the West of Scotland Primary Prevention Study: a nested case–control study. Lancet 369(9556):107–114PubMedCrossRefGoogle Scholar
- 21.Huber M, Voller H, Jakob S, Reibis R, Do V, Bolbrinker J, Zergibel I, Schmieder RE, Treszl A, Wegscheider K et al (2010) Role of the angiotensin II type 2 receptor gene (+1675G/A) polymorphism on left ventricular hypertrophy and geometry in treated hypertensive patients. J Hypertens 28(6):1221–1229PubMedCrossRefGoogle Scholar
- 22.No authors listed (1999) 1999 World Health Organization-International Society of Hypertension Guidelines for the Management of Hypertension. Guidelines Subcommittee. J Hypertens 17(2):151–183Google Scholar
- 29.Benjamini Y, Hochberg Y (1995) Controlling the false discovery rate: a new and powerful approach to multiple testing. Journal of the Royal Statistical Society B 57:1289–1300Google Scholar
- 30.de Simone G, Devereux RB, Daniels SR, Koren MJ, Meyer RA, Laragh JH (1995) Effect of growth on variability of left ventricular mass: assessment of allometric signals in adults and children and their capacity to predict cardiovascular risk. J Am Coll Cardiol 25(5):1056–1062PubMedCrossRefGoogle Scholar
- 35.Lang R, Bierig M, Devereux R, Flachskampf FA, Foster E, Pellikka P, Picard MH, Prather A, Roman MJ, Shanewise J et al (2006) Recommendations for chamber quantification. A report from the American Society of Echocardiography’s Nomenclature and Standards Committee, the Task Force on Chamber Quantification, and the European Association of Echocardiography. Eur J Echocardiogr 7(2):79–108PubMedCrossRefGoogle Scholar