Genetic variants of tumor necrosis factor-α and its levels: A correlation with dyslipidemia and type 2 diabetes susceptibility. Issue 3 (June 2019)

• Record Type: Journal Article
• Authors: Patel, Roma; Palit, Sayantani Pramanik; Rathwa, Nirali; Ramachandran, A.V.; Begum, Rasheedunnisa
• Is Part Of: Clinical nutrition. Volume 38:Issue 3(2019)
• Page Start: 1414
• Page End: 1422
• Publication Date: 2019-06
• Subjects: Type 2 diabetes -- Tumor necrosis factor-α -- Single nucleotide polymorphism -- Free fatty acid -- Genotype–phenotype correlation -- Visceral adipose tissue; TNF Tumor Necrosis Factor-α -- FFA Free Fatty Acid -- TC Total Cholesterol -- TG Triglycerides -- LDL Low Density Lipoprotein -- HDL High Density Lipoprotein -- PCR-RFLP Polymerase Chain Reaction-Restriction Fragment Length Polymorphism; Critically ill -- Nutrition -- Periodicals; Diet therapy -- Periodicals; Parenteral feeding -- Periodicals; Enteral feeding -- Periodicals; Enteral Nutrition -- Periodicals; Parenteral Nutrition -- Periodicals; Metabolism -- Periodicals; Diétothérapie -- Périodiques; Alimentation parentérale -- Périodiques; Alimentation entérale -- Périodiques; Nutrition -- Périodiques; Diet therapy; Enteral feeding; Nutrition; Parenteral feeding; Electronic journals; Periodicals; Electronic journals; 615.854
• DOI: 10.1016/j.clnu.2018.06.962
• Languages: English
• ISSNs: 0261-5614

Abstract

Summary: 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.