Lack of association between the-308 polymorphism of the tumor necrosis factor-alpha gene and the insulin resistance syndrome

Background: Previous studies have demonstrated a role for tumor necrosis fa ctor-alpha (TNF-alpha) in insulin resistance, A polymorphic variant of the TNF-alpha gene, the TNF2 allele, which is a guanine to adenine polymorphism at position -308 in the TNF-alpha promoter, is associated with higher basa l and inducible promoter activity. The present study examined whether the T NF2 allele was associated with altered levels of different components of th e insulin resistance syndrome, clustering of these components, or the 10-ye ar change in the level of these components. Methods: Components of the insulin resistance syndrome included insulin res istance, as determined by fasting insulin levels, body mass index, systolic blood pressure, triglycerides, uric acid, and high density lipoprotein-cho lesterol. The study population was a subsample of participants from the Cor onary Artery Risk Development in (Young) Adults (CARDIA) study, which inclu ded African American and white men and women aged 18-30. The sample include d 243 black women, 142 black men, 392 white women, and 386 white men. Subje cts mere typed at the TNF-alpha locus. Results: The frequency of the TNF2 allele was 12% in blacks and 16% in whit es. Age-adjusted levels of the different components examined were not diffe rent at either baseline or year 10 in carriers of the TNF2 allele versus ho mozygotes for the wild-type allele, and the 10-year change In the level of different components was not different between the two genotype groups. The re also was no evidence of increased clustering of components of the insuli n resistance syndrome in carriers of the TNF2 allele. Moreover, there was n o evidence of an association between the TNF2 allele and clustering across quartiles of BMI or quartiles of dietary fat intake (ie, Key's score). Conclusions: In African Americans and whites, neither the TNF2 allele nor a nother polymorphism in the TNF-alpha gene or a neighboring gene with which the TNF2 allele is In linkage disequilibrium is associated with differences in the level of or increased clustering of components of the insulin resis tance syndrome.