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

• Published in: Clinical chemistry (Baltimore, Md.) Md.), 2006-01, Vol.52 (1), p.97
• Main Authors: Gonzalez-Sanchez, Jose L, Martinez-Calatrava, Maria J, Martinez-Larrad, Maria T, Zabena, Carina, Fernandez-Perez, Cristina, Laakso, Markku, Serrano-Rios, Manuel
• Format: Article
• Language: English
• Subjects: Adipocytes; Body mass index; Cholesterol; Diabetes; Genotypes; Glucose; Homeostasis; Insulin resistance; Metabolism; Mutation; Obesity; Plasma; Polymorphism; Tumor necrosis factor-TNF
• ISSN: 0009-9147; 1530-8561
• DOI: 10.1373/clinchem.2005.049452

We investigated whether interactions of the -308G/A polymorphism in the promoter region of the tumor necrosis factor-alpha (TNF-alpha) gene with single-nucleotide polymorphisms (SNPs) 45 and 276 of the adiponectin gene are associated with circulating adiponectin and soluble TNF-alpha receptor 2 (sTNFR2) concentrations in a Spanish population. 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). The 2-h postload glucose and serum insulin concentrations were higher in -308A allele carriers than in -308G/G individuals homozygous for the TNF-alpha 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-alpha -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 (beta = -0.090; P = 0.005) than individuals without these genotypes. 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-alpha gene and SNP 45 in the adiponectin gene.