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.
BACKGROUND
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.


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-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.


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-alpha gene and SNP 45 in the adiponectin gene.
González-Sánchez
José L
JL
Department of Internal Medicine II, Hospital Clínico San Carlos, Madrid, Spain.
Martínez-Calatrava
María J
MJ
Martínez-Larrad
María T
MT
Zabena
Carina
C
Fernández-Pérez
Cristina
C
Laakso
Markku
M
Serrano-Ríos
Manuel
M
D000005:Abdomen / Q000033:anatomy & histology; D052242:Adiponectin / Q000097:blood / Q000235:genetics*; D000328:Adult; D000368:Aged; D000886:Anthropometry; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000097:blood; D005260:Female; D005838:Genotype; D005951:Glucose Tolerance Test; D006579:Heterozygote; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood; D044967:Serum; D012995:Solubility; D013030:Spain; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D049629:Waist-Hip Ratio
D052242:Adiponectin; D007328:Insulin; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha