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

Abstract Tumor necrosis factor-α (TNF-α) polymorphisms may influence dyslipidemia, 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 dyslipidemia in 595 participants (162 cases, 433 controls) from the Chaoshan region of China. Anthropometric, biochemical, and genetic data were analyzed using Chi-squared 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 dyslipidemia. Carriers of the TC+CC genotype for -1031T/C (odds ratio [OR]=0.48, 95% CI: 0.30-0.78, P FDR =0.006) and the CA+AA genotype for -863C/A (OR=0.41, 95% CI: 0.24-0.70, P FDR =0.004) had lower odds of dyslipidemia. Protective effects were observed for the C allele at -1031T/C (OR=0.58, P FDR =0.012) and the A allele at -863C/A (OR=0.47, P FDR =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 dyslipidemia, particularly in males, and provides mechanistic insights into their role in transcriptional regulation.