Polymorphisms in the leptin receptor gene, body composition and fat distribution in overweight and obese women.
OBJECTIVE
Leptin is an adipocyte-secreted hormone involved in body weight regulation, acting through the leptin receptor, localised centrally in the hypothalamus as well as peripherally, amongst others on adipose tissue. The aim of this study was to evaluate whether polymorphisms in the leptin receptor (LEPR) gene were related to obesity and body fat distribution phenotypes, such as waist and hip circumferences and the amount of visceral and subcutaneous fat.


METHODS
Three known LEPR polymorphisms, Lys109Arg, Gln223Arg and Lys656Asn, were typed on genomic DNA of 280 overweight and obese women (body mass index (BMI)>25), aged 18-60 y. General linear model (GLM) analyses were performed in 198 pre- and 82 postmenopausal women, adjusting the data for age and menopausal state, plus fat mass for the fat distribution phenotypes.


RESULTS
No associations were found between the LEPR polymorphisms and BMI or fat mass. In postmenopausal women, carriers of the Asn656 allele had increased hip circumference (P=0.03), total abdominal fat (P=0.03) and subcutaneous fat (P=0.04) measured by CT scan. Total abdominal fat was also higher in Gln223Gln homozygotes (P=0.04). Also in postmenopausal women, leptin levels were higher in Lys109Lys homozygotes (P=0.02).


CONCLUSIONS
In conclusion, polymorphisms in the leptin receptor gene are associated with levels of abdominal fat in postmenopausal overweight women. Since body fat distribution variables were adjusted for fat mass, these results suggest that DNA sequence variations in the leptin receptor gene play a role in fat topography and may be involved in the predisposition to abdominal obesity.
Wauters
M
M
Department of Endocrinology, Metabolism and Clinical Nutrition, University Hospital Antwerp, Antwerp, Belgium.
Mertens
I
I
Chagnon
M
M
Rankinen
T
T
Considine
R V
RV
Chagnon
Y C
YC
Van Gaal
L F
LF
Bouchard
C
C
D000273:Adipose Tissue / Q000033:anatomy & histology*; D000293:Adolescent; D000328:Adult; D000483:Alleles; D001823:Body Composition; D015992:Body Mass Index; D002352:Carrier Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D020738:Leptin / Q000235:genetics; D008593:Menopause; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D044465:White People / Q000235:genetics
D002352:Carrier Proteins; C515448:LEPR protein, human; D020738:Leptin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin