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 factor-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 basal and inducible promoter activity. The present study examined whether the TNF2 allele was associated with altered levels of different components of the insulin resistance syndrome, clustering of these components, or the 10-year change in the level of these components.


METHODS
Components of the insulin resistance syndrome included insulin resistance, as determined by fasting insulin levels, body mass index, systolic blood pressure, triglycerides, uric acid, and high density lipoprotein-cholesterol. The study population was a subsample of participants from the Coronary Artery Risk Development in (Young) Adults (CARDIA) study, which included African American and white men and women aged 18-30. The sample included 243 black women, 142 black men, 392 white women, and 386 white men. Subjects were typed at the TNF-alpha locus.


RESULTS
The frequency of the TNF2 allele was 12% in blacks and 16% in whites. Age-adjusted levels of the different components examined were not different at either baseline or year 10 in carriers of the TNF2 allele versus homozygotes for the wild-type allele, and the 10-year change in the level of different components was not different between the two genotype groups. There also was no evidence of increased clustering of components of the insulin resistance syndrome in carriers of the TNF2 allele. Moreover, there was no evidence of an association between the TNF2 allele and clustering across quartiles of BMI or quartiles of dietary fat intake (i.e., Key's score).


CONCLUSIONS
In African Americans and whites, neither the TNF2 allele nor another 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 resistance syndrome.
da Sliva
B
B
Department of Medicine, Northwestern University Medical School, Chicago, Ill. 60611, USA.
Gapstur
S M
SM
Achenbach
Y H
YH
Schuh
T S
TS
Kotlar
T J
TJ
Liu
K
K
Lowe
W L
WL
D000293:Adolescent; D000328:Adult; D000483:Alleles; D015992:Body Mass Index; D005260:Female; D005838:Genotype; D006801:Humans; D007333:Insulin Resistance; D008137:Longitudinal Studies; D008297:Male; D011110:Polymorphism, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha