Obesity, oxidative DNA damage and vitamin D as predictors of genomic instability in children and adolescents

Abstract

Background/objectives Epidemiological evidence indicates obesity in childhood and adolescence to be an independent risk factor for cancer and premature mortality in adulthood. Pathological implications from excess adiposity may begin early in life. Obesity is concurrent with a state of chronic inflammation, a well-known aetiological factor for DNA damage. In addition, obesity has been associated with micro-nutritional deficiencies. Vitamin D has attracted attention for its anti-inflammatory properties and role in genomic integrity and stability. The aim of this study was to determine a novel approach for predicting genomic instability via the combined assessment of adiposity, DNA damage, systemic inflammation, and vitamin D status. Subjects/methods We carried out a cross-sectional study with 132 participants, aged 10–18, recruited from schools and paediatric obesity clinics in London. Anthropometric assessments included BMI Z-score, waist and hip circumference, and body fat percentage via bioelectrical impedance. Inflammation and vitamin D levels in saliva were assessed by enzyme-linked immunosorbent assay. Oxidative DNA damage was determined via quantification of 8-hydroxy-2′-deoxyguanosine in urine. Exfoliated cells from the oral cavity were scored for genomic instability via the buccal cytome assay. Results As expected, comparisons between participants with obesity and normal range BMI showed significant differences in anthropometric measures (p < 0.001). Significant differences were also observed in some measures of genomic instability (p < 0.001). When examining relationships between variables for all participants, markers of adiposity positively correlated with acquired oxidative DNA damage (p < 0.01) and genomic instability (p < 0.001), and negatively correlated with vitamin D (p < 0.01). Multiple regression analyses identified obesity (p < 0.001), vitamin D (p < 0.001), and oxidative DNA damage (p < 0.05) as the three significant predictors of genomic instability. Conclusions Obesity, oxidative DNA damage, and vitamin D deficiency are significant predictors of genomic instability. Non-invasive biomonitoring and predictive modelling of genomic instability in young patients with obesity may contribute to the prioritisation and severity of clinical intervention measures.

The impact of AIM2 inflammasome-induced pyroptosis on acute gouty arthritis and asymptomatic hyperuricemia patients

“…The accumulation of DNA damage, particularly in response to high-fat diets ( 30 , 31 ), is further supported by the presence of γH2AX foci, an early indicator of DNA double-strand breaks ( 32 ). Additionally, the correlation between overweight status in adolescents and lymphocytic DNA damage ( 33 ) and the association of obesity with various DNA lesions, including double-strand breaks and oxidative base damage, which are reflective of BMI and DNA damage indices ( 29 ), align with our observations. In the AHU group, significantly elevated dsDNA levels were observed compared to the HC group (see Figure 1 ), which is consistent with the metabolic syndrome phenotype characterized by obesity, dyslipidemia, and mild inflammation (see Table 1 , Figure 4 ).…”

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“…The association between DNA/RNA damage and chromosomal aberration has been documented. Usman et al confirmed that oxidative DNA damage in obese children is a predictor of genomic instability [ 38 , 39 ].…”

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“…DNA repair deficiencies have been linked to aging, suggesting that interventions reducing the mutational nuclear or mitochondrial load and enhancing or rerouting repair mechanisms may slow aging and delay the onset of age-related diseases. VitD emerges as a potential intervention in this context [ 18 ].…”