title: Leukocyte telomere shortening in grown-up patients with congenital heart disease.
abstract: OBJECTIVE
  Children with congenital heart disease are exposed by repeated imaging to ionizing radiation, which may have important implications for lifetime health risks. Leukocyte telomere length (LTL), a reliable biomarker of genomic instability, is associated with increased risk of cancer and cardiovascular disease. We investigated LTL in grown-up patients with CHD (GUCHs) and a positive history of medical radiation exposure as well as the influence of functional polymorphisms of genes involved in DNA repair.
  
  
  METHODS
  A group of 50 GUCH patients (26 males; age 25.2 ± 9.0 years) and 50 healthy age/gender-matched subjects (20 males; 27.0 ± 3.1 years) were enrolled. In GUCH patients, the cumulative exposure was estimated as effective dose (ED) in milliSievert. LTL was measured by quantitative RT-PCR. X-ray repair cross complementing-1 (XRCC1) and X-ray repair cross complementing-3 (XRCC3) SNPs (XRCC1Arg399Gln, XRCC1Arg194Tr and XRCC3 Thr241Met) were evaluated.
  
  
  RESULTS
  GUCHs showed significantly shorter LTL compared with controls (1.0 ± 0.3 vs 1.3 ± 0.4, p = 0.001). A significant inverse correlation between LTL and cumulative radiological ED was observed (r = -0.34, p = 0.03). Patients with Thr/Met XRCC3 or Met/Met XRCC3 genotypes were significantly associated with a significantly shorter LTL compared with wild-type genotype (p = 0.01 for Thr/Met and p = 0.008 for Met/Met). Carriers of XRCC1 194Trp and XRCC3 241Met alleles presented a significant interaction with cumulative radiation dose exposure for LTL (both p interaction = 0.02).
  
  
  CONCLUSIONS
  GUCH patients have LTL shortening, suggesting evidence of early biological aging. Common SNPs in DNA repair genes modify the effects of medical exposure to radiation LTL-related degenerative diseases.
authors.affiliation: CNR, Institute of Clinical Physiology, Pisa, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Vecoli
authors.affiliation: CNR, Institute of Clinical Physiology, Pisa, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Borghini
authors.affiliation: CNR, Institute of Clinical Physiology, Massa, Italy.
authors.forename: Ilenia
authors.initials: I
authors.lastname: Foffa
authors.affiliation: CNR, Institute of Clinical Physiology, Massa, Italy.
authors.forename: Lamia
authors.initials: L
authors.lastname: Ait-Ali
authors.affiliation: CNR, Institute of Clinical Physiology, Pisa, Italy.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Picano
authors.affiliation: CNR, Institute of Clinical Physiology, Pisa, Italy. Electronic address: mariagrazia.andreassi@ifc.cnr.it.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Andreassi
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D006330:Heart Defects, Congenital / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D006801:Humans; D007962:Leukocytes / Q000502:physiology* / Q000528:radiation effects*; D008297:Male; D000069079:Radiation Exposure / Q000009:adverse effects*; D059506:Telomere Shortening / Q000502:physiology* / Q000528:radiation effects*; D055815:Young Adult
keywords: Congenital heart disease; GUCH; Genetic polymorphisms; Ionizing radiation; Telomere length