A polymorphism in the leptin promoter region (-2548 G/A) influences gene expression and adipose tissue secretion of leptin.
Horm Metab Res
; 34(7): 355-9, 2002 Jul.
Article
in En
| MEDLINE
| ID: mdl-12189581
ABSTRACT
There is a large inter-individual variation in circulating leptin concentrations at each level of body fat content. The reason for this is unknown. We investigated whether a polymorphism in the promoter region of the leptin gene (-2548G/A) influences gene transcription and leptin expression in 39 non-obese female subjects. Eleven subjects were homozygous for the AA genotype, 18 were heterozygous (GA) and 10 carried the GG genotype. AA subjects had higher levels of serum leptin than did GA/GG subjects (14.5 +/- 2.1 vs. 9.7 +/- 0.9 ng/ml, p = 0.02). Adipose tissue leptin secretion rate in AA subjects was twice as high as in GA/GG subjects:
1158 +/- 288 vs. 626 +/- 84 ng/2 h/10 (7) cells (p = 0.02). These differences were also statistically significant with leptin levels adjusted for body mass index (p = 0.03 - 0.04). Adipose tissue leptin mRNA levels were 60 % higher in AA subjects, as compared to GA/GG subjects, 74 +/- 10 vs. 46 +/- 4 amol/ micro g RNA (p = 0.01). EMSA revealed that nuclear extracts derived from both U937 cells and human adipocytes form a protein-DNA complex with the leptin -2548G/A polymorphic site and bind with higher affinity to the -2548A-site. In conclusion, a common polymorphism in the promoter of the human leptin gene (-2548G/A) influences leptin expression, possibly at the transcriptional level, and therefore also adipose secretion levels of the hormone.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Polymorphism, Genetic
/
Gene Expression
/
Adipose Tissue
/
Promoter Regions, Genetic
/
Leptin
Limits:
Adult
/
Female
/
Humans
Language:
En
Journal:
Horm Metab Res
Year:
2002
Document type:
Article