Association of TNF-α 308 G/A Polymorphism With Type 2 Diabetes: A Case–Control Study in the Iranian Kurdish Ethnic Group

Abstract

ObjectivesTumor necrosis factor-α (TNF-α) plays roles in the development of obesity, insulin resistance, and possibility of Type 2 diabetes mellitus (T2DM). The objective of the current study was to evaluate the association of TNF-α promoter−308 G/A polymorphism with T2DM.MethodsIn all, 1038 patients with T2DM and 1023 normoglycemic controls were included in this study. All participants were genotyped using the polymerase chain reaction-restriction fragment length polymorphism method. Genotypic and allelic frequencies were then analyzed in each group. Serum lipids, fasting glucose, fasting serum insulin, homeostatic model assessment of insulin resistance, and hemoglogin A1c levels were determined by conventional methods.ResultsThe allelic frequency of the A allele was significantly different between case and control participants (p = 0.006). Genotypes GA and AA were found to be significantly associated with 2.24- and 3.18-fold increased risk for T2DM, respectively. Similarly, the dominant model of -308 G/A polymorphism was found to have a higher risk for T2DM (odds ratio = 2.34, p = 0.001). Individuals with T2DM carrying the GA + AA genotypes of -308 G/A variation had significantly lower fasting plasma insulin than those carrying GG genotype.ConclusionOur findings revealed that there is an association between the TNF-α promoter -308 G/A polymorphism and T2DM in this population.

Adiponectin (+276 G/T), Tumor Necrosis Factor-alpha (-308 G/A) and Interleukin-6 (-174 C/G) Genes Polymorphisms in Egyptian Type 2 Diabetic Patients

“…Furthermore, association of the GA/AA genotype and A allele with T2DM was observed in Egyptian diabetic patients. The current results greed with the findings of previous studies that revealed significantly higher GA/AA genotype and A allele frequencies among Chinese [41], French [42], Scandinavian [15], Germans [43] and Australians [44] populations.…”

“…Because TNF-α can impair insulin signal pathways and lead to β cell destruction, increased TNF-α is considered to play a central role in the development of T2DM [40]. So far, many studies have focused on the association between -308 G/A TNF-α promoter polymorphism and T2DM, but the results were still controversial [15,16].…”

“…Many studies have shown that SNP at position -308 G/A was associated with various inflammatory conditions including T2DM [14]. It is reported that -308 G/A polymorphism associates with either increased or decreased insulin resistance in patients with T2DM and patients without diabetes [15]. Because of controversial reports from several populations, there is still no definitive evidence of the association between this variation and risk for T2DM [16].…”

IL-6, TNF-α, and IL-10 levels/polymorphisms and their association with type 2 diabetes mellitus and obesity in Brazilian individuals

“…Some studies have investigated the association among TNF-α, IL-6, and IL-10 gene polymorphisms with metabolic diseases (17)(18)(19)(20)(21)(22)(23)(24)(25). Despite these reports examining the association of inflammation markers and SNPs in cytokine genes, much controversy remains as to their role in diabetes occurrence (26)(27)(28)(29)(30)(31)(32)(33)(34).…”

Study of the associations between polymorphic markers rs1800629 TNFa, rs909253 Lta, rs767455 TNFR1, rs1061624 TNFR2 and the development of type 2 diabetes

“…Однако результаты работ, посвященных изучению связей генов-кандидатов факторов некроза опухоли и их рецепторов с развитием СД2, неодно-значны в разных популяциях. Так, например, показано, что аллель А rs1800629TNF является фактором риска формирования СД2 в иранской (OR=2,34) [10], индий-ской (OR=3,21) [11] и бразильской (OR=1,82) [12] по-пуляциях. Среди населения Хорватии и Венгрии данных ассоциаций выявлено не было [13], а в популяции Мек-сики установлено, что фактором риска развития СД2 яв-ляется генотип GGrs1800629 TNF (OR=3,64) [14].…”