Key result
A common variant in the TTN gene was significantly associated with a low cardiorespiratory fitness level (OR 3.55) in childhood acute lymphoblastic leukemia survivors.
Why the study?
Childhood acute lymphoblastic leukemia treatments cause long-term cardiac toxicity, but associations between genetic variants and cardiorespiratory fitness had not been studied in survivors.
Are genetic variants in trainability genes associated with cardiorespiratory fitness levels in childhood acute lymphoblastic leukemia survivors?
Cross-Sectional (n=239)
No
Are genetic variants in trainability genes associated with cardiorespiratory fitness levels in childhood acute lymphoblastic leukemia survivors?
Odds Ratio: 3.55 (95% CI 1.66–7.63)
p-value: p=0.0005
Genetic variants in trainability genes, particularly TTN, LEPR, IGFBP1, ENO3, and SLC22A16, are associated with lower cardiorespiratory fitness in childhood ALL survivors, suggesting a role for genetic profiling in personalized post-treatment follow-up.
Genetic variants tied to fitness in ALL survivors; leaves open clinical utility pending replication and prospective validation.
BACKGROUND: The progress of treatments of childhood acute lymphoblastic leukemia (ALL) has made it possible to reach a survival rate superior to 80%. However, the treatments lead to several long-term adverse effects, including cardiac toxicity. Although studies have reported associations between genetic variants and cardiorespiratory fitness, none has been performed on childhood ALL survivors. METHODS: We performed whole-exome sequencing in 239 childhood ALL survivors from the PETALE cohort. Germline variants (both common and rare) in selected set of genes (N = 238) were analyzed for an association with cardiorespiratory fitness. RESULTS: Our results showed that the common variant in the TTN gene was significantly associated with a low cardiorespiratory fitness level (p = 0.0005) and that the LEPR, IGFBPI and ENO3 genes were significantly associated with a low cardiorespiratory fitness level in female survivors (p ≤ 0.002). Also, we detected an association between the low cardiorespiratory fitness level in participants that were stratified to the "high risk" prognostic group and functionally predicted rare variants in the SLC22A16 gene (p = 0.001). Positive associations between cardiorespiratory fitness level and trainability genes were mainly observed in females. CONCLUSIONS: For the first time, we observed that low cardiorespiratory fitness in childhood ALL survivors can be associated with variants in genes related to subjects' trainability. These findings could allow better childhood ALL patient follow-up tailored to their genetic profile and cardiorespiratory fitness, which could help reduce at least some of the burden of long-term adverse effects of treatments.
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Caru et al. (2019) conducted a cross-sectional in Childhood acute lymphoblastic leukemia (ALL) survivors (n=239). TTN gene minor allele (rs6723526) vs. TTN gene major allele was evaluated on Low cardiorespiratory fitness level (< 83.8% predicted VO2 peak) (OR 3.55, 95% CI 1.66-7.63, p=0.0005). A common variant in the TTN gene was significantly associated with a low cardiorespiratory fitness level (OR 3.55) in childhood acute lymphoblastic leukemia survivors.
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