PMID- 29980311 OWN - NLM STAT- MEDLINE DCOM- 20200601 LR - 20200601 IS - 1532-1983 (Electronic) IS - 0261-5614 (Linking) VI - 38 IP - 3 DP - 2019 Jun TI - Genetic variants of tumor necrosis factor-alpha and its levels: A correlation with dyslipidemia and type 2 diabetes susceptibility. PG - 1414-1422 LID - S0261-5614(18)31181-6 [pii] LID - 10.1016/j.clnu.2018.06.962 [doi] AB - BACKGROUND & AIM: Tumor necrosis factor-alpha (TNF-alpha) 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-alpha and its association with altered TNF-alpha transcript levels and plasma concentrations ii) free fatty acid (FFA) concentrations as a marker for dyslipidemia and its association with TNF-alpha 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-alpha levels. TNF-alpha and FFA concentrations were estimated from plasma samples by ELISA. RESULTS: Our study suggests: i) involvement of TNF-alpha -857 C/T in T2D patients (p < 0.0001), ii) 2.072 and 6.7 fold elevation in TNF-alpha transcript levels in patients' PBMCs and adipose tissues respectively, increased plasma TNF-alpha (p = 0.0122) particularly in obese patients (p = 0.0405), increased plasma FFA (p = 0.0215) and, iii) association of TNF-alpha -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-alpha 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-alpha along with elevated TNF-alpha and FFA concentrations play a role in the development of dyslipidemia which could be a potent risk factor towards T2D in Gujarat population. CI - Copyright (c) 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved. FAU - Patel, Roma AU - Patel R AD - Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, 390002, Gujarat, India. FAU - Palit, Sayantani Pramanik AU - Palit SP AD - Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, 390002, Gujarat, India. FAU - Rathwa, Nirali AU - Rathwa N AD - Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, 390002, Gujarat, India. FAU - Ramachandran, A V AU - Ramachandran AV AD - Department of Zoology, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, 390002, Gujarat, India. FAU - Begum, Rasheedunnisa AU - Begum R AD - Department of Biochemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, 390002, Gujarat, India. Electronic address: rasheedunnisab@yahoo.co.in. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180623 PL - England TA - Clin Nutr JT - Clinical nutrition (Edinburgh, Scotland) JID - 8309603 RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Adult MH - Diabetes Mellitus, Type 2/*blood/genetics MH - Dyslipidemias/*blood/genetics MH - Female MH - Genetic Association Studies/*methods MH - Humans MH - Male MH - Middle Aged MH - Polymorphism, Single Nucleotide/*genetics MH - Tumor Necrosis Factor-alpha/*blood/*genetics OTO - NOTNLM OT - Free fatty acid OT - Genotype-phenotype correlation OT - Single nucleotide polymorphism OT - Tumor necrosis factor-alpha OT - Type 2 diabetes OT - Visceral adipose tissue EDAT- 2018/07/08 06:00 MHDA- 2020/06/02 06:00 CRDT- 2018/07/08 06:00 PHST- 2018/01/08 00:00 [received] PHST- 2018/06/04 00:00 [revised] PHST- 2018/06/13 00:00 [accepted] PHST- 2018/07/08 06:00 [pubmed] PHST- 2020/06/02 06:00 [medline] PHST- 2018/07/08 06:00 [entrez] AID - S0261-5614(18)31181-6 [pii] AID - 10.1016/j.clnu.2018.06.962 [doi] PST - ppublish SO - Clin Nutr. 2019 Jun;38(3):1414-1422. doi: 10.1016/j.clnu.2018.06.962. Epub 2018 Jun 23.