PMID- 9287048
OWN - NLM
STAT- MEDLINE
DCOM- 19970925
LR  - 20190515
IS  - 0012-1797 (Print)
IS  - 0012-1797 (Linking)
VI  - 46
IP  - 9
DP  - 1997 Sep
TI  - The TNF-alpha gene Nco I polymorphism influences the relationship among insulin 
      resistance, percent body fat, and increased serum leptin levels.
PG  - 1468-72
AB  - Tumor necrosis factor-alpha (TNF-alpha), acting as a modulator of gene expression 
      in adipocytes, is implicated in the development of insulin resistance and 
      obesity. The aim of this study was to investigate whether the Nco I polymorphism 
      of the TNF-alpha gene influences the relationship among insulin resistance, 
      percent body fat, and serum leptin levels. A sample of 38 subjects (19 men, mean 
      age 36.2 +/- 1.9 years, BMI 28.8 +/- 1.2 kg/m2, range 22.2-35.7; and 19 women, 
      age 34.9 +/- 1.4 years, BMI 28.1 +/- 0.8 kg/m2, range 19-37.9) was divided into 
      two groups on the basis of the Nco I genotype. Twenty-three subjects were (+/+) 
      homozygotes for the presence of the Nco I restriction site that is associated 
      with a guanine at position -308 of the TNF-alpha promoter. Of the other subjects, 
      12 were (+/-) heterozygotes and 3 (-/-) homozygotes for the absence of the 
      restriction site, resulting from a guanine-to-adenine substitution at position 
      -308 of the TNF-alpha promoter. This substitution (termed TNF-2) leads to higher 
      rate of transcription of TNF-alpha than the wild-type allele TNF-1 in vitro. 
      TNF-1 (+/+) and TNF-2 (+/- and -/-) groups of subjects were comparable in sex, 
      age, BMI, waist-to-hip ratio, and several skinfold measurements. Basal serum 
      insulin was greater (14.2 +/- 2 vs. 9.2 +/- 0.9 mU/l, P = 0.041) in the TNF-2 
      group in the presence of comparable serum glucose concentration. The integrated 
      area under the curve of serum insulin concentrations, measured in response to a 
      75-g oral glucose challenge, and the percent body fat, measured by bioelectric 
      impedance, were significantly increased in TNF-2 subjects (226.8 +/- 33 vs. 139.4 
      +/- 17.8 mU/l, P = 0.032; 33.6 +/- 2.8 vs. 24.9 +/- 2%, P = 0.01). TNF-2 subjects 
      also showed a decreased insulin sensitivity index, as determined by the 
      frequently sampled intravenous glucose tolerance test with minimal model analysis 
      (1.9 +/- 0.4 vs. 3.05 +/- 0.3 min(-1) x mU(-1) x l(-1), P = 0.03). These 
      differences were more marked among women. Paralleling the known relationship 
      between insulin and leptin levels, serum leptin concentration was clearly 
      increased in the TNF-2 group (19.6 +/- 3.4 vs. 11.1 +/- 1.5 ng/ml, P = 0.03). 
      Therefore, (+/-) heterozygotes and (-/-) homozygotes may be more susceptible to 
      developing insulin resistance and increased percent body fat. Results of the 
      present study suggest that TNF-alphaNco I polymorphism may exacerbate the 
      alterations in leptin levels normally found among insulin-resistant subjects.
FAU - Fernandez-Real, J M
AU  - Fernandez-Real JM
AD  - Department of Endocrinology, University Hospital of Girona Dr. Josep Trueta, 
      Spain.
FAU - Gutierrez, C
AU  - Gutierrez C
FAU - Ricart, W
AU  - Ricart W
FAU - Casamitjana, R
AU  - Casamitjana R
FAU - Fernandez-Castaner, M
AU  - Fernandez-Castaner M
FAU - Vendrell, J
AU  - Vendrell J
FAU - Richart, C
AU  - Richart C
FAU - Soler, J
AU  - Soler J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Diabetes
JT  - Diabetes
JID - 0372763
RN  - 0 (Leptin)
RN  - 0 (Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 3.1.21.- (endodeoxyribonuclease NcoI)
RN  - EC 3.1.21.4 (Deoxyribonucleases, Type II Site-Specific)
SB  - IM
MH  - Adult
MH  - *Body Composition
MH  - Body Mass Index
MH  - Deoxyribonucleases, Type II Site-Specific/*metabolism
MH  - Female
MH  - Gene Expression Regulation
MH  - Humans
MH  - *Insulin Resistance
MH  - Leptin
MH  - Male
MH  - Polymorphism, Restriction Fragment Length
MH  - Proteins/*metabolism
MH  - Tumor Necrosis Factor-alpha/*genetics
EDAT- 1997/09/01 00:00
MHDA- 1997/09/01 00:01
CRDT- 1997/09/01 00:00
PHST- 1997/09/01 00:00 [pubmed]
PHST- 1997/09/01 00:01 [medline]
PHST- 1997/09/01 00:00 [entrez]
AID - 10.2337/diab.46.9.1468 [doi]
PST - ppublish
SO  - Diabetes. 1997 Sep;46(9):1468-72. doi: 10.2337/diab.46.9.1468.