Brief reportTumor necrosis factor alpha −238G/A (rs 361525) gene polymorphism predicts progression to type-2 diabetes in an Eastern Indian population with prediabetes
Introduction
Individuals with prediabetes (IPD) have a high annual risk of progression to type-2 diabetes (DM) (2.5–18%) [1]. Proinflammatory cytokines like tumor necrosis factor-α (TNFα) and interleukin-6 (IL6) interfere with insulin signaling (inhibits phosphorylation of insulin receptor substrates), induce endoplasmic reticulum and mitochondrial stress and activation of nuclear factor kappa B, causing pancreatic beta cell apoptosis [2], [3].
Single nucleotide based polymorphism (SNP) study in the promoter region of TNFα (−238 and −308) and IL6 (−174) have suggested their role in increased IR and diabetes complications [4], [5]. No study has evaluated these SNPs in IPD. This study aimed to evaluate the relationship of these SNPs with body mass index (BMI), IR in normal individuals (NI) and IPD, and their effect on prediabetes progression.
Section snippets
Materials and methods
Individuals attending health camps conducted across the city of Kolkata and relatives of patients with diabetes attending the diabetic clinic were screened by finger prick blood glucose estimation (Accu-Chek® Active, Roche, India). Individuals with impaired fasting glucose (IFG; 100–125 mg/dl) or postprandial/random blood glucose between 140 and 199 mg/dl were called on separate day for 75 g oral glucose tolerance test (OGTT). Individuals with IFG or impaired glucose tolerance (IGT; 140–199 mg/dl)
Results
One hundred twenty-two IPD and 100 NI were studied. The baseline characteristics have been elaborated in Table 1. No significant departure from HWE was observed for IL6 −174G/C (rs 1800795), TNFα −308 G/A (1800629) and −238 G/A (rs 361525) variant in IPD (χ2 = 0.804, P = 0.369; χ2 = 0.400, P = 0.527; χ2 = 1.07, P = 0.300 respectively) or NI (χ2 = 0.531, P = 0.466; χ2 = 0.147, P = 0.702; χ2 = 0.1071; P = 0.743 respectively).
There was no significant difference in the allelic distribution of IL-6 −174G/C and −308 TNFα
Discussion
Studies have suggested that −238 G/A polymorphism has a role in increased IR, type-2 DM [4], and proliferative diabetic retinopathy [9]. Others have found no relation with obesity and cardiovascular disease [5]. Some have suggested protective effect of this polymorphism against verbal memory impairment in diabetes [10]. Similarly, TNFα −G308A and IL6 −G174C SNPs studies have shown mixed outcomes [11], [12], [13], [14], [15], [16], [17], [18]. Ethnicity, heterogeneous study population and
Conflict of interest
There are no conflicts of interest.
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