Abstract
Obesity is associated with inflammation, which can disturb genome stability. Tumor necrosis factor (TNF-α) polymorphism was found to affect TNF-α protein production and inflammation. Therefore, the present study illustrates the relationship between TNF-α polymorphism, the degree of inflammation assessed by serum high sensitivity C-reactive protein concentration (CRP-hs) and basal DNA damage in patients with obesity (BMI 30–34.9 kg/m2) and control subjects with proper body mass (BMI < 25 kg/m2). A total of 115 participants (75 obese premenopausal women; and 40 age-, and gender-matched controls) were included. Biochemical parameters (serum concentrations of total-cholesterol, HDL-cholesterol, LDL- cholesterol, triglycerides, glucose, apolipoprotein AI, CRP-hs) and endogenous DNA damage (determined by comet assay) were measured. TNF-α G-308A polymorphism (rs1800629) was analyzed by PCR-RFLP (PCR-restriction fragments length polymorphism). An effect of TNF-α genotype on serum CRP-hs concentration was noted (p = 0.031). In general, carriers of the rare A allele of the TNF-α G-308A polymorphism had significantly lower endogenous DNA damage and serum CRP-hs concentrations than GG homozygotes, however, the protective effect of the A allele was especially visible in non-obese women. Serum CRP-hs concentrations and levels of DNA damage (% DNA in tail) were significantly higher in obese than in controls (p = 0.001 and p < 0.0001, respectively). The adjusted multiple linear regression analyses revealed a significant, independent impact of obesity on DNA damage (p = 0.00000) and no effect of other covariates i.e. age, TNF-α genotype and serum CRP-hs concentration. Our study showed that obesity has a significant impact on the levels of endogenous DNA damage. Obesity abolished the protective effect of A allele of the TNF-α G-308A polymorphism on DNA damage and on inflammation development observed in non-obese A allele carriers.
Highlights
Smoking, improper diet and environmental toxins have been recognized as main exogenous sources of DNA damage [1]
That is a result of an imbalance between energy intake and expenditure, has reached epidemic proportions with increasing prevalence worldwide
The human TNF-α protein is coded by the gene located near major histocompatibility complex (MHC) between the class I HLA-B and the class II HLA-DR loci [70, 71]
Summary
Improper diet and environmental toxins have been recognized as main exogenous sources of DNA damage [1]. Besides exogenous factor-caused DNA breaks, endogenous DNA damage and failure of DNA repair can disturb cell metabolism and function [2]. DNA damage has been found to be involved in aging and development of common diseases including cancer, atherosclerosis, metabolic syndrome [4,5,6]. The Comet Assay is a sensitive and low-cost technique, which measures DNA damage in individual cells [7, 8]. In addition to DNA strand breaks (double strand breaks and single strand breaks), the modified Comet Assay serve to detect oxidized bases, interstrand cross-links or
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