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

• Published in: Clinical nutrition (Edinburgh, Scotland) Vol. 38; no. 3; pp. 1414 - 1422
• Main Authors: Patel, Roma, Palit, Sayantani Pramanik, Rathwa, Nirali, Ramachandran, A.V., Begum, Rasheedunnisa
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.06.2019
• Subjects: Free fatty acid; Genotype–phenotype correlation; Single nucleotide polymorphism; Tumor necrosis factor-α; Type 2 diabetes; Visceral adipose tissue; Type 2 diabetes; FFA; Visceral adipose tissue; Tumor necrosis factor-α; Free fatty acid; Genotype–phenotype correlation; PCR-RFLP; TNF; TC; HDL; TG; LDL; Single nucleotide polymorphism
• ISSN: 0261-5614; 1532-1983
• DOI: 10.1016/j.clnu.2018.06.962

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. 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. 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). 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.