GENETIC-VARIABILITY IN THE TNF-ALPHA PROMOTER IS NOT ASSOCIATED WITH TYPE-II DIABETES-MELLITUS (NIDDM)

Recent evidence suggests that expression of tumor necrosis factor-alph a (TNF-alpha) by adipocytes is a molecular mediator of insulin resista nce in obesity. We have therefore tested the hypothesis that variation s within the regulatory region of the TNF-alpha gene, which might caus e increased adipocyte or generalized TNF-alpha synthesis, are associat ed with NIDDM, a state in which insulin resistance is routinely observ ed. Neither the previously known variants within the TNF-alpha promote r at position -308 and -238, nor two newly identified polymorphisms at position -376 and -163, were found at a significantly higher frequenc y in Caucasian NIDDM patients compared to non-diabetic controls. No ge netic variants were found in Pima Indians. These data make it unlikely that mutations within regulatory elements of the TNF-alpha gene are a ssociated with an increase in the prevalence of NIDDM. (C) 1995 Academ ic Press, Inc.