Abstract
Study Model/Methodology: This is a cross-sectional study with a sample of 104 overweight/obese adolescents, with a mean weight of 52.98 kg ± 22.00, mean age 16.01 ± 2.91 years. We used the homeostasis model assessment-estimated IR (HOMA-IR) index to quantify the insulin resistance (IR). The -308 polymorphism of the promoter of TNF-α was performed using polymerase chain reactionrestriction fragment length polymorphism technique. Statistical analysis of the quantitative measures was conducted with a student’s t-test. For correlation between the genotype and alleles, we used chisquare statistical test. To test the heterogeneity between HOMA-IR and the anthropometric parameters the Mann-Whitney test was used, associated with the Hardy-Weinberg equilibrium. The association between -308G/A polymorphism of the promoter of TNF-α and HOMA-IR was tested by univariate linear regression analysis. Objective: Investigate the association between -308G/A polymorphism in the promoter of tumor necrosis factor-alpha (TNF-α) and susceptibility to IR in overweight/obese adolescents. Results: The prevalence of IR was 18.30% according to the HOMA-IR. The frequency of GG, AG and AA genotype was found 75 (72.12%), 28 (26.92%) and 1.0 (0.96%) respectively. Allele frequencies for guanine (G) and adenine (A) were 178 (85.58%) and 30 (14.42%), respectively. The allele A as well as GA and AA genotype contributed to increase RI (14.42% and 27.88% respectively). Conclusion: The - 308 G/A polymorphism of the promoter of TNF-α can contribute to the IR increase in obese adolescents with GA and AA genotypes.
Highlights
Tumor necrosis factor-alpha (TNF-α) is a potent central mediator and pro-inflammatory cytokine implicated in the immunological response that has been associated with a large number of human diseases.[1,2] The activation of the immune system during infection or injury leads to widespread metabolic changes
There is a trend on increasing secretion of cytokines that has been implicated in the etiology of insulin resistance (IR) and other components of the metabolic syndrome, such as glucose intolerance, obesity, dyslipidemia, and high blood pressure.[3]
The polymorphism at position -308 in the promoter region of the TNF-α gene may lead to its increased transcription in adipocytes, and involving a single base change (-308 G/A), in the promoter region, this variant have been linked to IR and obesity in different ethnic groups.[6]
Summary
Tumor necrosis factor-alpha (TNF-α) is a potent central mediator and pro-inflammatory cytokine implicated in the immunological response that has been associated with a large number of human diseases.[1,2] The activation of the immune system during infection or injury leads to widespread metabolic changes. One would be oxidative stress and inflammatory changes resulting from glucose and macronutrient intake, and the other concerns the increased concentrations of TNF-α itself which would interfere with insulin action by suppressing insulin signal transduction This might interfere with the anti-inflammatory effect of insulin, which in turn might promote inflammation.[5] The polymorphism at position -308 in the promoter region of the TNF-α gene may lead to its increased transcription in adipocytes, and involving a single base change (-308 G/A), in the promoter region, this variant have been linked to IR and obesity in different ethnic groups.[6] It is important to note that the TNF-α gene is located in the chromosomal region 6p21.1-21.3, next to the major histocompatibility complex.[7]
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