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.

中文翻译：

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肥胖女性的TNF-αG-308A遗传变异，血清CRP-hs浓度和DNA损伤。

肥胖与发炎有关，发炎会干扰基因组的稳定性。发现肿瘤坏死因子（TNF-α）多态性影响TNF-α蛋白的产生和炎症。因此，本研究说明了肥胖患者（BMI 30-34.9 kg / m2）中TNF-α多态性，通过血清高敏C反应蛋白浓度（CRP-hs）评估的炎症程度和基础DNA损伤之间的关系。并控制体重适当的受试者（BMI <25 kg / m2）。总共包括115名参与者（75名肥胖的绝经前妇女； 40名年龄和性别匹配的对照组）。测量了生化参数（总胆固醇，HDL-胆固醇，LDL-胆固醇，甘油三酸酯，葡萄糖，载脂蛋白AI，CRP-hs的血清浓度）和内源性DNA损伤（通过彗星试验确定）。通过PCR-RFLP（PCR-限制性片段长度多态性）分析TNF-αG-308A多态性（rs1800629）。注意到TNF-α基因型对血清CRP-hs浓度的影响（p ＝ 0.031）。通常，与GG纯合子相比，TNF-αG-308A多态性的罕见A等位基因的携带者具有较低的内源性DNA损伤和血清CRP-hs浓度，但是，非肥胖中A等位基因的保护作用尤其明显女人。肥胖者的血清CRP-hs浓度和DNA损伤水平（尾部DNA百分比）显着高于对照组（分别为p = 0.001和p <0.0001）。调整后的多元线性回归分析显示，肥胖对DNA损伤具有显着的独立影响（p = 0.00000），而对年龄，TNF-α基因型和血清CRP-hs浓度等其他协变量没有影响。我们的研究表明，肥胖对内源性DNA损伤的水平有重要影响。肥胖消除了在非肥胖A等位基因携带者中观察到的TNF-αG-308A多态性A等位基因对DNA损伤和炎症发展的保护作用。