Increased abdominal obesity, insulin and glucose levels in nondiabetic subjects with a T29C polymorphism of the transforming growth factor-beta1 gene.
BACKGROUND
In humans, a T-->C transition at nucleotide 29 in the region encoding the signal peptide sequence of the transforming growth factor (TGF)-beta(1), which results in a Leu-->Pro substitution at codon 10, has been associated with myocardial infarction.


OBJECTIVE
In the present study, we genotyped 284 unrelated, nondiabetic Swedish men born in 1944 to assess the impact of the Leu10Pro variant on obesity, including abdominal obesity, and estimates of insulin, glucose and lipid metabolism as well as blood pressure.


RESULTS
The frequency of the Pro10 variant was 38.9% (95% CI 32.2-46.0%), and the distribution of genotypes was in Hardy-Weinberg equilibrium. Data analysis showed that heterozygotes had significantly higher body mass index compared to homozygous carriers to the Leu10 variant. In addition, homozygous carriers of the Leu10 variant had significantly lower abdominal sagittal diameter than both Leu10Pro and Pro10Pro carriers. We also found that heterozygotes had significantly higher fasting insulin values as well as higher HOMA insulin-resistance index in comparison to homozygous carriers of the Leu10. Fasting glucose levels were significantly higher in subjects with the Pro10Pro variant compared to subjects with either the Leu10Leu or Leu10Pro variant.


CONCLUSIONS
These findings suggest that the Pro10 allele in the TGF-beta(1) gene pathway might contribute to prevalent diseases such as obesity and type 2 diabetes mellitus.
Rosmond
Roland
R
Department of Clinical Chemistry, Sahlgrenska University Hospital, Göteborg, Sweden.
Chagnon
Monique
M
Bouchard
Claude
C
Björntorp
Per
P
D000005:Abdomen / Q000473:pathology*; D000225:Adenine; D001786:Blood Glucose / Q000032:analysis*; D005215:Fasting / Q000097:blood; D005787:Gene Frequency; D014644:Genetic Variation; D006147:Guanine; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000473:pathology* / Q000503:physiopathology; D011110:Polymorphism, Genetic / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics*; D053773:Transforming Growth Factor beta1
D001786:Blood Glucose; D007328:Insulin; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D006147:Guanine; D000225:Adenine