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G-308A Polymorphism of the Tumor Necrosis Factor Gene Promoter and Salivary Cortisol Secretion¹

Department of Heart and Lung Diseases (R.R., P.B.), Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden; and Pennington Biomedical Research Center (R.R., M.C., C.B.), Baton Rouge, Louisiana 70808

Address all correspondence and requests for reprints to: Roland Rosmond, M.D., Ph.D., Department of Heart and Lung Diseases, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden.

The objective of the current study was to examine the potential impact of the GA substitution at position -308 of the tumor necrosis factor (TNF-) gene promoter on obesity and estimates of insulin, glucose, and lipid metabolism as well as circulating hormones including salivary cortisol in 284 unrelated Swedish men born in 1944. The subjects were genotyped by using PCR amplification of the 5' untranslated region of the TNF- gene followed by digestion with the restriction enzyme NcoI. The frequencies were 0.77 for allele G and 0.23 for allele A. Tests for differences in salivary cortisol levels between the TNF- genotypes revealed that there were significantly higher cortisol levels in the morning, before as well as 30 and 60 min after stimulation by a standardized lunch in homozygotes for the rare allele in comparison with the other genotypes. In addition, homozygotes for the rare allele had a tendency toward higher mean values of body mass index, waist to hip ratio, and abdominal sagittal diameter compared with the other genotype groups. The results also indicated a weak trend toward elevated insulin and glucose levels among men with the A/A genotype. In conclusion, a GA polymorphism in the 5' untranslated region of the TNF- gene is associated with elevated morning cortisol levels as well as elevated postprandial cortisol secretion. This increase in cortisol secretion might be the endocrine mechanism underlying the previously observed associations between the NcoI TNF- polymorphism and obesity as well as insulin resistance. However, to what extent this polymorphism is associated with these conditions is uncertain from the present data.