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.
A group of 50 GUCH patients (26 males; age 25.2±9.0years) and 50 healthy age/gender-matched subjects (20 males; 27.0±3.1years) 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.
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 pinteraction=0.02).
Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
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.