Genetic variants of tumor necrosis factor-α and its levels: A correlation with dyslipidemia and type 2 diabetes susceptibility

Abstract

Background & aim: Tumor necrosis factor-α (TNF-α) and its genetic variants are implicated in the development of type 2 diabetes (T2D) as a result of systemic inflammation, dyslipidemia, and insulin resistance. The aim of the present study was to investigate i) single nucleotide polymorphisms (SNPs) of TNF-α and its association with altered TNF-α transcript levels and plasma concentrations ii) free fatty acid (FFA) concentrations as a marker for dyslipidemia and its association with TNF-α and iii) genotype-phenotype correlation analysis in T2D patients.

Methods: Plasma and PBMCs were separated from venous blood of 478 diabetic patients and 502 age-matched non-diabetic individuals. Genomic DNA was isolated from PBMCs and RNA was isolated from PBMCs and adipose tissue samples. PCR-RFLP was used for genotyping and qPCR to estimate TNF-α levels. TNF-α and FFA concentrations were estimated from plasma samples by ELISA.

Results: Our study suggests: i) involvement of TNF-α -857 C/T in T2D patients (p < 0.0001), ii) 2.072 and 6.7 fold elevation in TNF-α transcript levels in patients' PBMCs and adipose tissues respectively, increased plasma TNF-α (p = 0.0122) particularly in obese patients (p = 0.0405), increased plasma FFA (p = 0.0215) and, iii) association of TNF-α -238 G/A with body mass index (BMI) (p = 0.0270) and, -857 C/T with fasting blood glucose (FBG) (p = 0.0122) and triglycerides (TG) (p = 0.0015). Correlation analysis suggests that TNF-α concentrations are positively correlated with BMI (r = 0.3, p = 0.04) and negatively correlated with HDL (r = -0.39, p = 0.001) while the FFA concentrations are positively correlated with BMI (r = 0.35, p = 0.0004).

Conclusion: It can be concluded that the genetic variant of TNF-α along with elevated TNF-α and FFA concentrations play a role in the development of dyslipidemia which could be a potent risk factor towards T2D in Gujarat population.

Keywords: Free fatty acid; Genotype–phenotype correlation; Single nucleotide polymorphism; Tumor necrosis factor-α; Type 2 diabetes; Visceral adipose tissue.