Association analysis of G-2548A and A19G polymorphisms in the human leptin gene with
obesity
Tomas Z1, Smolej Narancic N1, Barbalic M1, Zajc M1, Skaric-Juric T1, Rudan P1, Rudan I2,
Campbell H3, Wright AF4
1
Institute for Anthropological Research, Zagreb, Croatia
“Andrija Stampar” School of Public Health, School of Medicine, University of Zagreb,
Zagreb, Croatia
3
Department of Public Health Sciences, University of Edinburgh, Medical School,
Edinburgh, UK
4
MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK
2
Leptin is a protein hormone which plays an important role in the regulation of body adiposity,
lipid metabolism and reproductive function. It is primarily secreted by the adipocytes and its
concentration in the blood is proportional to the amount of body fat. Many leptin gene
polymorphisms have been found, but their association with obesity is still controversial. We
tested the polymorphisms G-2548A in promoter region and A19G in intron 1 of leptin gene for
association with leptin concentration in the blood and obesity. A population-based association
study was conducted in the population isolate of the Eastern Adriatic island of Vis, Croatia.
Three hundred and twenty randomly selected subjects from the Vis population were
genotyped. Obesity was defined as BMI≥30 kg/m2. The results revealed significant
association of G-2548A variant and leptin concentration in a codominant pattern (p=0.026).
The ancestral G allele which displays as a minor allele in the Vis population (frequency of
0.44) was associated with higher leptin levels. The leptin concentration was significantly
higher in the obese (60.1 ng/ml, N=244), than in the non-obese group (20.7 ng/ml, N=76) and
it was more than three times higher in women (44.0 ng/ml) compared to men. However, no
association of G-2548A and A19G polymorphisms with obesity was found (with leptin
concentration, sex and age as covariates). The results indicate that the studied polymorphisms
are not relevant markers for common obesity in this isolated population, but were found to
influence the leptin concentration which is an obesity-related phenotype.
Key words: leptin, polymorphism, isolated populations
Topic: No. 7 – Normal variation, population genetics, genetic epidemiology
Mode of presentation: POSTER