TNF-α G-308A genetic variants, serum CRP-hs concentration and DNA damage in obese women

Obesity is associated with inflammation, which can disturb genome stability. Tumor necrosis factor (TNF-alpha) polymorphism was found to affect TNF-alpha protein production and inflammation. Therefore, the present study illustrates the relationship between TNF-alpha 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/m(2)) and control subjects with proper body mass (BMI<25 kg/m(2)). 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-alpha G-308A polymorphism (rs1800629) was analyzed by PCR-RFLP (PCR-restriction fragments length polymorphism). An effect of TNF-alpha genotype on serum CRP-hs concentration was noted (p=0.031). In general, carriers of the rare A allele of the TNF-alpha 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-alpha 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-alpha G-308A polymorphism on DNA damage and on inflammation development observed in non-obese A allele carriers.