Interaction of the −308G/A Promoter Polymorphism of the Tumor Necrosis Factor-α Gene with Single-Nucleotide Polymorphism 45 of the Adiponectin Gene: Effect on Serum Adiponectin Concentrations in a Spanish Population

Abstract

Background: We investigated whether interactions of the −308G/A polymorphism in the promoter region of the tumor necrosis factor-α (TNF-α) gene with single-nucleotide polymorphisms (SNPs) 45 and 276 of the adiponectin gene are associated with circulating adiponectin and soluble TNF-α receptor 2 (sTNFR2) concentrations in a Spanish population. Methods: We performed anthropometric and physiologic measurements in 809 unrelated participants recruited with a simple random sampling approach from respondents to a cross-sectional population-based epidemiologic survey in the province of Segovia in central Spain (Castille). Results: The 2-h postload glucose and serum insulin concentrations were higher in −308A allele carriers than in −308G/G individuals homozygous for the TNF-α gene. Plasma concentrations of sTNFR2 were positively correlated with body mass index, waist-to-hip ratio, and sagittal abdominal diameter among individuals with type 2 diabetes. Individuals with type 2 diabetes and the −308A allele had higher sTNFR2 and lower adiponectin concentrations than −308G homozygotes. Moreover, individuals carrying both the TNF-α −308A allele and the G allele of SNP 45 in the adiponectin gene had the highest prevalence of impaired glucose tolerance (adjusted odds ratio, 1.26; 95% confidence interval, 1.01–1.56; P = 0.038) and had lower adiponectin concentrations (β = −0.090; P = 0.005) than individuals without these genotypes. Conclusions: Our findings are the first to indicate that a higher incidence of impaired glucose tolerance and low circulating adiponectin concentration may be associated with interaction between the −308G/A promoter polymorphism of the TNF-α gene and SNP 45 in the adiponectin gene.