[The mechanism of tumor necrosis factor-alpha (TNF-alpha) induced insulin resistance by variation in promoter region of TNF-alpha gene].
OBJECTIVE
To investigate the relationship between the G to A variant at the--308 bp of the promoter region of tumor necrosis factor-alpha gene (TNF-alpha-P) and the body adiposity, the insulin secretion and action, and the glucose and lipid levels in Chinese population.


METHODS
359 Chinese were genotyped for the TNF-alpha-P by using PCR/Nco I digestion. Fasting blood lipid profile and the levels of plasma glucose (PG), insulin (INS), c-peptide (CP) and the free fatty acids (FFA) at 0, 1/2, 1, 2 and 3 hours after glucose challenge were measured.


RESULTS
Genotype frequencies of TNF-alpha-P were not associated with diabetes and obesity. The genotype frequency of the G/A heterozygotes was significantly increased in non-diabetic subgroups with less decreased levels of 2 h-FFA and AUC-FFA after glucose challenge (Fisher exact P = 0.002 and 0.041 respectively). The FFA levels in non-diabetics with G/A heterozygotes were higher than those with G/G homozygotes, especially in the comparisons of the 2 h and 3 h FFA levels after glucose challenge (P = 0.029 and 0.030 respectively). Similar tendency was also observed in diabetics.


CONCLUSIONS
Circulation FFA level reflects the degree of lipolysis in adipose tissue. The difference in the degree of lipolysis led by the variant of the promoter region of TNF-alpha may be one of the mechanisms for the variation in the degree of insulin resistance in general population.
Fang
Q
Q
Department of Medical Genetics Research Laboratory, Shanghai Sixth People's Hospital, Shanghai 200233.
Xiang
K
K
Lu
J
J
D000328:Adult; D000368:Aged; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D005230:Fatty Acids, Nonesterified; D014409:Tumor Necrosis Factor-alpha