Pharmacogenetics and genomics, 2017-12, Vol.27 (12), p.445-453
2017
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- Autor(en) / Beteiligte
- Titel
- Exome array analysis identifies GPR35 as a novel susceptibility gene for anthracycline-induced cardiotoxicity in childhood cancer
- Ist Teil von
- Pharmacogenetics and genomics, 2017-12, Vol.27 (12), p.445-453
- Ort / Verlag
- United States
- Erscheinungsjahr
- 2017
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Pediatric cancer survivors are a steadily growing population; however, chronic anthracycline-induced cardiotoxicity (AIC) is a serious long-term complication leading to considerable morbidity. We aimed to identify new genes and low-frequency variants influencing the susceptibility to AIC for pediatric cancer patients. We studied the association of variants on the Illumina HumanExome BeadChip array in 83 anthracycline-treated pediatric cancer patients. In addition to single-variant association tests, we carried out a gene-based analysis to investigate the combined effects of common and low-frequency variants to chronic AIC. Although no single-variant showed an association with chronic AIC that was statistically significant after correction for multiple testing, we identified a novel significant association for G protein-coupled receptor 35 (GPR35) by gene-based testing, a gene with potential roles in cardiac physiology and pathology (P=7.0×10), which remained statistically significant after correction for multiple testing (PFDR=0.03). The greatest contribution to this observed association was made by rs12468485, a missense variant (p.Thr253Met, c.758C>T, minor allele frequency=0.04), with the T allele associated with an increased risk of chronic AIC and more severe symptomatic cardiac manifestations at low anthracycline doses. Using exome array data, we identified GPR35 as a novel susceptibility gene associated with chronic AIC in pediatric cancer patients.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1744-6872eISSN: 1744-6880DOI: 10.1097/FPC.0000000000000309Titel-ID: cdi_crossref_primary_10_1097_FPC_0000000000000309
- Format
- –
- Schlagworte
- Adolescent, Anthracyclines - adverse effects, Antineoplastic Agents - adverse effects, Child, Child, Preschool, Exome, Female, Genetic Predisposition to Disease, Heart - drug effects, Humans, Infant, Leukemia - drug therapy, Leukemia - physiopathology, Male, Osteosarcoma - complications, Osteosarcoma - drug therapy, Receptors, G-Protein-Coupled - genetics, Sarcoma, Ewing - complications, Sarcoma, Ewing - drug therapy