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%; p raw = 0.008, p mt = 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%; p raw = 0.002, p mt = 0.018; rs1151026, G allele −1.9%, CI = −3.0% to −0.8%; p raw < 0.001, p mt = 0.002) with the extension that a frequent haplotype in BICD1 showed an absolute −1.8% (CI = −3.0% to −0.7%; p raw = 0.002, p mt = 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.
Institute of Clinical Pharmacology and Toxicology, CharitéCentrum für Therapieforschung, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. matthias.huber@charite.de
Matthias
M
Huber
Andras
A
Treszl
Markus
M
Wehland
Ingke
I
Winther
Irina
I
Zergibel
Rona
R
Reibis
Juliane
J
Bolbrinker
Monika
M
Stoll
Gilbert
G
Schönfelder
Karl
K
Wegscheider
Heinz
H
Völler
Reinhold
R
Kreutz
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000368:Aged; D000375:Aging; D000483:Alleles; D002318:Cardiovascular Diseases / Q000150:complications* / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D015331:Cohort Studies; D003598:Cytoskeletal Proteins / Q000235:genetics; D004452:Echocardiography; D005260:Female; D005838:Genotype; D006352:Heart Ventricles / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000235:genetics*; D007962:Leukocytes / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D060888:Real-Time Polymerase Chain Reaction; D016615:Telomere / Q000235:genetics* / Q000473:pathology; D016277:Ventricular Function, Left
D048868:Adaptor Proteins, Signal Transducing; C109571:BICD1 protein, human; D003598:Cytoskeletal Proteins