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The Journal of Clinical Endocrinology & Metabolism Vol. 85, No. 4 1731-1734
Copyright © 2000 by The Endocrine Society

Comments

The -238 and -308 G->A Polymorphisms of the Tumor Necrosis Factor {alpha} Gene Promotor Are Not Associated with Features of the Insulin Resistance Syndrome or Altered Birth Weight in Danish Caucasians1

Søren K. Rasmussen, Søren A. Urhammer, Jan N. Jensen, Torben Hansen, Knut Borch-Johnsen and Oluf Pedersen

Steno Diabetes Center and Hagedorn Research Institute (S.K.R., S.A.U., J.N.J., T.H., O.P.), DK-2820, Gentofte, Denmark; and Center of Preventive Medicine (K.B.-J.), Glostrup University Hospital, DK-2600, Glostrup, Denmark

Address correspondence and requests for reprints to: Søren K. Rasmussen, M.Sc., Steno Diabetes Center, Niels Steensens Vej 2, DK-2820 Gentofte, Denmark.

Abstract

Recently, two G->A polymorphisms at positions -308 and -238, in the promoter of the tumor necrosis factor {alpha} (TNF-{alpha}) gene, have been identified. These variants have, in different ethnic groups, been linked to estimates of insulin resistance and obesity. The objective of the present study was to investigate whether these genetic variants of TNF-{alpha} were associated with features of the insulin resistance syndrome or alterations in birth weight in two Danish study populations comprising 380 unrelated young healthy subjects and 249 glucose-tolerant relatives of type 2 diabetic patients, respectively. All study participants underwent an iv glucose tolerance test with the addition of tolbutamide after 20 min. In addition, a number of biochemical and anthropometric measures were performed on each subject. The subjects were genotyped for the polymorphisms by applying PCR restriction fragment length polymorphism. Neither of the variants was related to altered insulin sensitivity index or other features of the insulin resistance syndrome (body mass index, waist to hip ratio, fat mass, fasting serum lipids or fasting serum insulin or C-peptide). Birth weight and the ponderal index were also not associated with the polymorphisms. In conclusion, although the study was carried out on sufficiently large study samples, the study does not support a major role of the -308 or -238 substitutions of the TNF-{alpha} gene in the pathogenesis of insulin resistance or altered birth weight among Danish Caucasian subjects.




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