A Study Of The Association Of Tumor Necrosis Factor-αPolymorphisms And Obesity And Insulin Resistance

Background:Insulin resistance plays a crucial role in the developing of metabolic syndrome. Common disorders, such as obesity, dyslipidemia, polycystic ovarian syndrome, etc. contribute to the progression of endothelial dysfunction and cardiovascular diseases. And insulin resistance is considered to be the basic pathological mechanism of this progress. Although the exact causes of insulin resistance remain unknown, many genetic and environmental factors contribute to its occurrence. In recent decades, several studies have found that TNF-α participates in obesity-related insulin resistance.TNF-α promoter polymorphisms have received great interest because they are considered to alter TNF-a gene transcription and protein production. However, reports for these polymorphisms have failed in reaching a consensus. In light of this inconsistence, a reevaluation is necessary in for the influence of TNF-α variants on obesity and insulin resistance.Purpose:To evaluate the influence of TNF-α promoter polymorphisms on data reported on BMI, risk of obesity, plasma glucose levels, plasma insulin levels, and HOMA-IR. Methods:We carried out a systematic literature search for articles published prior to Mar3,2013on the association between TNF-a variants and obesity and/or insulin resistance. According to the defined inclusion/exclusion criteria, we determine the eligible studies and extract measurements related to obesity and insulin resistance:BMI and risk of obesity, fasting plasma glucose levels, fasting plasma insulin levels and HOMA. We use the Review Manager5.1and Stata11.0sofrware to conduct the meta-analysis.Results:According to the inclusion/exclusion criteria,16articles (18studies) were included in the meta-analysis. These studies are divided into several subgroups according to ethnicities and BMI.1. Over all, TNF-α G-308A variant was significantly associated with increased insulin levels (SMDFE=0.12,95%CI:0.03-0.20). Exclusion of studies deviating from HWE did not alter the pattern of results (SMDFE=0.13,95%CI:0.03-0.22). In the analysis stratified by ethnicity, significant association remained in Caucasians (SMDFE=0.13,95%CI:0.04-0.22), but not in East Asians (SMDFE=0.21,95%CI:-0.32-0.74). Interestingly, the result of subgroup analysis showed an increased trend in the pooled SMD from low to high BMI levels (Low BMI:SMDFE=0.03,95%CI:-0.16-0.21; varying BMI:SMDFE=0.12,95%CI:-0.03-0.27; High BMI:SMDFE=0.16,95%CI:0.03-0.29), with significant result only observed in obese subgroup. Cumulative meta-analysis under the dominant model showed a trend of association between TNF-α G-308A polymorphism and insulin as evidence accumulated.2. For Caucasians, TNF-a G-308A variant was significantly associated with increased HOMA (WMDFE=0.49,95%CI:0.03-0.94). However, this trend is not remained in the analysis of all studies or East Asians.3. TNF-α G-308A variant was not significantly associated with increased BMI, risk of obesity or glucose levels.4. TNF-α G-238A variant was not significantly associated with increased BMI, glucose levels, insulin levels or HOMA-IR. Conclusion:TNF-α G-308A polymorphism is associated with elevated insulin levels by interacting with high BMI.