Hostname: page-component-54dcc4c588-br6xx Total loading time: 0 Render date: 2025-10-06T13:26:07.021Z Has data issue: false hasContentIssue false
  • English
  • Français

TNF-α –1031T/C and –863C/A polymorphisms are associated with dyslipidaemia

Published online by Cambridge University Press:  31 July 2025

Kaihao Lin ,
Chaofen Wu ,
Xin Yao  and
Xianbin Cai Open the ORCID record for Xianbin Cai [Opens in a new window]
Kaihao Lin
Affiliation:
Department of Gastroenterology, The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong, People’s Republic of China
Chaofen Wu
Affiliation:
Department of Gastroenterology, The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong, People’s Republic of China Department of Pathology, The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong, People’s Republic of China
Xin Yao
Affiliation:
Department of Gastroenterology, The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong, People’s Republic of China
Xianbin Cai*
Affiliation:
Department of Gastroenterology, The First Affiliated Hospital of Shantou University Medical College, Shantou 515041, Guangdong, People’s Republic of China
*
Corresponding author: Xianbin Cai; Email: cxbin1@qq.com
Get access Rights & Permissions [Opens in a new window]

Abstract

TNF-α polymorphisms may influence dyslipidaemia, but their role remains unclear. This case–control study investigated associations between TNF-α gene polymorphisms (–1031T/C, −863C/A, −857C/T, −308G/A and −238G/A) and dyslipidaemia in 595 participants (162 cases, 433 controls) from the Chaoshan region of China. Anthropometric, biochemical and genetic data were analysed using χ2 tests and logistic regression, with the false discovery rate (FDR) method applied to correct for multiple comparisons. Results revealed that only the −1031T/C and −863C/A polymorphisms were significantly associated with dyslipidaemia. Carriers of the TC + CC genotype for −1031T/C (OR = 0·48; 95 % CI: 0·30, 0·78; PFDR = 0·006) and the CA + AA genotype for −863C/A (OR = 0·41; 95 % CI: 0·24, 0·70; PFDR = 0·004) had lower odds of dyslipidaemia. Protective effects were observed for the C allele at −1031T/C (OR = 0·58, PFDR = 0·012) and the A allele at −863C/A (OR = 0·47, PFDR = 0·004). Stratified analyses showed that these associations were significant in males but not females. Functional annotation linked these TNF-α gene polymorphisms to transcription factors (e.g. HNF-1A, STAT1β) in the adipogenesis pathway. This study reveals genetic associations between TNF-α polymorphisms and dyslipidaemia, particularly in males, and provides mechanistic insights into their role in transcriptional regulation.

Keywords

DyslipidaemiaTNF-αSNPGenetic association

Information

Type
Research Article
Information
British Journal of Nutrition , Volume 134 , Issue 3 , 14 August 2025 , pp. 177 - 185
Check for updates
Copyright
© The Author(s), 2025. Published by Cambridge University Press on behalf of the Nutrition Society

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

References

Joint Committee for Guideline Revision (2018) 2016 Chinese guidelines for the management of dyslipidemia in adults. J Geriatr Cardiol 15, 1–29.Google Scholar
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (2001) Executive summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 285, 2486–2497.CrossRefGoogle Scholar
World Health Organization (2021) Noncommunicable Diseases: Risk Factors. The Global Health Observatory. https://www.who.int/data/gho/data/themes/topics/topic-details/GHO/ncd-risk-factors (accessed March 2025).Google Scholar
Lu, Y, Zhang, H, Lu, J, et al. (2021) Prevalence of dyslipidemia and availability of lipid-lowering medications among primary health care settings in China. JAMA Netw Open 4, e2127573.CrossRefGoogle ScholarPubMed
Willer, CJ, Schmidt, EM, Sengupta, S, et al. (2013) Discovery and refinement of loci associated with lipid levels. Nat Genet 45, 1274–1283.Google ScholarPubMed
Teslovich, TM, Musunuru, K, Smith, AV, et al. (2010) Biological, clinical and population relevance of 95 loci for blood lipids. Nature 466, 707–713.CrossRefGoogle ScholarPubMed
Pirillo, A, Casula, M, Olmastroni, E, et al. (2021) Global epidemiology of dyslipidaemias. Nat Rev Cardiol 18, 689–700.CrossRefGoogle ScholarPubMed
American Diabetes Association (2021) 10. Cardiovascular disease and risk management: standards of medical care in diabetes-2021. Diabetes Care 44, S125–S150. Addendum: Diabetes Care 44, 2183–2185.Google Scholar
Stevens, W, Peneva, D, Li, JZ, et al. (2016) Estimating the future burden of cardiovascular disease and the value of lipid and blood pressure control therapies in China. BMC Health Serv Res 16, 175.CrossRefGoogle ScholarPubMed
Papapanagiotou, A, Siasos, G, Kassi, E, et al. (2015) Novel inflammatory markers in hyperlipidemia: clinical implications. Curr Med Chem 22, 2727–2743.CrossRefGoogle ScholarPubMed
Hotamisligil, GS (2006) Inflammation and metabolic disorders. Nature 444, 860–867.CrossRefGoogle ScholarPubMed
Skoog, T, Eriksson, P, Hoffstedt, J, et al. (2001) Tumour necrosis factor-alpha (TNF-alpha) polymorphisms-857C/A and –863C/A are associated with TNF-α secretion from human adipose tissue. Diabetologia 44, 654–655.CrossRefGoogle ScholarPubMed
Sandoval-Pinto, E, Padilla-Gutiérrez, JR, Valdés-Alvarado, E, et al. (2016) Association of the –1031T>C polymorphism and soluble TNF-α levels with Acute Coronary Syndrome. Cytokine 78, 37–43.CrossRefGoogle ScholarPubMed
Kallel, A, Ftouhi, B, Jemaa, Z, et al. (2013) Tumor necrosis factor-α (TNF-α) –863C/A promoter polymorphism is associated with type 2 diabetes in Tunisian population. Diabetes Res Clin Pract 102, e24–e28.CrossRefGoogle ScholarPubMed
Guo, X, Li, C, Wu, J, et al. (2019) The association of TNF-α –308G/A and –238G/A polymorphisms with type 2 diabetes mellitus: a meta-analysis. Biosci Rep 39, BSR20191301.CrossRefGoogle ScholarPubMed
Cui, G, Wang, H, Li, R, et al. (2012) Polymorphism of tumor necrosis factor alpha (TNF-alpha) gene promoter, circulating TNF-α level, and cardiovascular risk factor for ischemic stroke. J Neuroinflammation 9, 235.CrossRefGoogle ScholarPubMed
Joffe, YT, van der Merwe, L, Evans, J, et al. (2012) The tumor necrosis factor-α gene –238G>A polymorphism, dietary fat intake, obesity risk and serum lipid concentrations in black and white South African women. Eur J Clin Nutr 66, 1295–1302.CrossRefGoogle ScholarPubMed
Yu, GI, Ha, E, Park, SH, et al. (2011) Association of tumor necrosis factor-α (TNF-α) promoter polymorphisms with overweight/obesity in a Korean population. Inflamm Res 60, 1099–1105.CrossRefGoogle Scholar
Park, HJ, Kim, SK, Park, HK, et al. (2017) Association of promoter polymorphism –857C/T (rs1799724) in tumor necrosis factor gene with intracerebral hemorrhage in Korean males. Neurol Res 39, 90–95.CrossRefGoogle ScholarPubMed
Messeguer, X, Escudero, R, Farré, D, et al. (2002) PROMO: detection of known transcription regulatory elements using species-tailored searches. Bioinf 18, 333–334.Google ScholarPubMed
Farré, D, Roset, R, Huerta, M, et al. (2003) Identification of patterns in biological sequences at the ALGGEN server: PROMO and MALGEN. Nucleic Acids Res 31, 3651–3653.CrossRefGoogle ScholarPubMed
Zhou, Y, Zhou, B, Pache, L, et al. (2019) Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat Commun 10, 1523.CrossRefGoogle ScholarPubMed
Faul, F, Erdfelder, E, Lang, AG, et al. (2007) G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods 39, 175–191.CrossRefGoogle Scholar
Bradley, JR (2008) TNF-mediated inflammatory disease. J Pathol 214, 149–160.CrossRefGoogle ScholarPubMed
Jovinge, S, Hamsten, A, Tornvall, P, et al. (1998) Evidence for a role of tumor necrosis factor α in disturbances of triglyceride and glucose metabolism predisposing to coronary heart disease. Metabolism 47, 113–118.CrossRefGoogle ScholarPubMed
Mahajan, A, Tabassum, R, Chavali, S, et al. (2010) Obesity-dependent association of TNF-LTA locus with type 2 diabetes in North Indians. J Mol Med 88, 515–522.CrossRefGoogle ScholarPubMed
Oki, E, Norde, MN, Carioca, AAF, et al. (2017) Polymorphisms of the TNF-α gene interact with plasma fatty acids on inflammatory biomarker profile: a population-based, cross-sectional study in São Paulo, Brazil. Br J Nutr 117, 1663–1673.CrossRefGoogle ScholarPubMed
Gomez-Delgado, F, Alcala-Diaz, JF, Garcia-Rios, A, et al. (2014) Polymorphism at the TNF-α gene interacts with Mediterranean diet to influence triglyceride metabolism and inflammation status in metabolic syndrome patients: from the CORDIOPREV clinical trial. Mol Nutr Food Res 58, 1519–1527.Google ScholarPubMed
Joffe, YT, Collins, M & Goedecke, JH (2013) The relationship between dietary fatty acids and inflammatory genes on the obese phenotype and serum lipids. Nutrients 5, 1672–1705.CrossRefGoogle ScholarPubMed
Ayelign, B, Genetu, M, Wondmagegn, T, et al. (2019) TNF-α (–308) gene polymorphism and type 2 diabetes mellitus in Ethiopian diabetes patients. Diabetes Metab Syndr Obes 12, 2453–2459.CrossRefGoogle ScholarPubMed
Ghareeb, D, Abdelazem, AS, Hussein, EM, et al. (2021) Association of TNF-α-308 G>A (rs1800629) polymorphism with susceptibility of metabolic syndrome. J Diabetes Metab Disord 20, 209–215.CrossRefGoogle ScholarPubMed
Phillips, CM, Goumidi, L, Bertrais, S, et al. (2010) Additive effect of polymorphisms in the IL-6, LTA, and TNF-{alpha} genes and plasma fatty acid level modulate risk for the metabolic syndrome and its components. J Clin Endocrinol Metab 95, 1386–1394.CrossRefGoogle ScholarPubMed
Wang, D, He, L & Zhang, X (2021) –308G/A polymorphism of tumor necrosis factor α (TNF-α) gene and metabolic syndrome susceptibility: a meta-analysis. Sci Rep 11, 3840.CrossRefGoogle ScholarPubMed
Duan, R, Wang, N, Shang, Y, et al. (2022) TNF-α (G-308A) polymorphism, circulating levels of TNF-α and IGF-1: risk factors for ischemic stroke-an updated meta-analysis. Front Aging Neurosci 14, 831910.CrossRefGoogle ScholarPubMed
Huang, R, Zhao, SR, Li, Y, et al. (2020) Association of tumor necrosis factor-α gene polymorphisms and coronary artery disease susceptibility: a systematic review and meta-analysis. BMC Med Genet 21, 29.CrossRefGoogle ScholarPubMed
Shen, Z, Munker, S, Wang, C, et al. (2014) Association between alcohol intake, overweight, and serum lipid levels and the risk analysis associated with the development of dyslipidemia. J Clin Lipidol 8, 273–278.CrossRefGoogle ScholarPubMed
Trapani, L & Pallottini, V (2010) Age-related hypercholesterolemia and HMG-CoA reductase dysregulation: sex does matter (a gender perspective). Curr Gerontol Geriatr Res 2010, 420139.CrossRefGoogle ScholarPubMed
Higuchi, T, Seki, N, Kamizono, S, et al. (1998) Polymorphism of the 5’-flanking region of the human tumor necrosis factor (TNF)-α gene in Japanese. Tissue Antigens 51, 605–612.CrossRefGoogle ScholarPubMed
Skoog, T, van’t Hooft, FM, Kallin, B, et al. (1999) A common functional polymorphism (C-->A substitution at position –863) in the promoter region of the tumour necrosis factor-α (TNF-alpha) gene associated with reduced circulating levels of TNF-alpha. Hum Mol Genet 8, 1443–1449.CrossRefGoogle Scholar
van Heel, DA, Udalova, IA, De Silva, AP, et al. (2002) Inflammatory bowel disease is associated with a TNF polymorphism that affects an interaction between the OCT1 and NF(-kappa)B transcription factors. Hum Mol Genet 11, 1281–1289.CrossRefGoogle ScholarPubMed
Kroeger, KM, Carville, KS & Abraham, LJ (1997) The –308 tumor necrosis factor-α promoter polymorphism effects transcription. Mol Immunol 34, 391–399.CrossRefGoogle ScholarPubMed
Louis, E, Franchimont, D, Piron, A, et al. (1998) Tumour necrosis factor (TNF) gene polymorphism influences TNF-α production in lipopolysaccharide (LPS)-stimulated whole blood cell culture in healthy humans. Clin Exp Immunol 113, 401–406.CrossRefGoogle ScholarPubMed
Kaluza, W, Reuss, E, Grossmann, S, et al. (2000) Different transcriptional activity and in vitro TNF-alpha production in psoriasis patients carrying the TNF-α 238A promoter polymorphism. J Invest Dermatol 114, 1180–1183.CrossRefGoogle ScholarPubMed
Supplementary material: File

Lin et al. supplementary material

Lin et al. supplementary material
Download Lin et al. supplementary material(File)
File 29.5 KB