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

¹ Department of Internal Medicine II, Hospital Clínico San Carlos, Madrid, Spain.
² Department of Medicine, University of Kuopio, Kuopio, Finland.

^aAddress correspondence to this author at: Department of Internal Medicine II, Hospital Clínico San Carlos, Cea Bermúdez 66, 5° G, 28003 Madrid, Spain. Fax 34-91-4429705; e-mail uinvest7.hcsc{at}salud.madrid.org.

Background: We investigated whether interactions of the –308G/A polymorphism in the promoter region of the tumor necrosis factor- (TNF-) gene with single-nucleotide polymorphisms (SNPs) 45 and 276 of the adiponectin gene are associated with circulating adiponectin and soluble TNF- 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- 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- –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 (ß = –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- gene and SNP 45 in the adiponectin gene.

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				C. Menzaghi, V. Trischitta, and A. Doria Genetic Influences of Adiponectin on Insulin Resistance, Type 2 Diabetes, and Cardiovascular Disease Diabetes, May 1, 2007; 56(5): 1198 - 1209. [Abstract] [Full Text] [PDF]