Leptin receptor Lys109Arg and Gln223Arg polymorphisms are associated with early atherosclerosis.
BACKGROUND
Leptin is a hormone expressed by the leptin gene, primarily in adipocytes, controlling food intake and energy expenditure. The effects of leptin are mediated by its receptor (LEPR) located in the central nervous system and other tissues, including adipocytes and endothelial cells. The aim of this study was to characterize two polymorphisms of LEPR, Lys109Arg (rs1137100) and Gln223Arg (rs1137101), as risk factors for early atherosclerosis. This connection has not been studied before.


METHODS
This study was performed in the randomly selected, middle-aged control subjects (n=526) from our well-defined OPERA (Oulu Project Elucidating Risk of Atherosclerosis) study. Analysis of covariance (ANCOVA) was performed to study the associations between genotypes, intima media thickness (IMT) measurements, and risk factors for atherosclerosis.


RESULTS
Subjects with the genotype Lys109Arg had the lowest body mass index (BMI) (P = 0.035), whereas Arg109Arg homozygotes had the highest total cholesterol (P=0.021) when adjusted for sex and age. Gln223Arg associated independently with systolic blood pressure (P=0.036). There were no differences in leptin concentrations between the genotypes. The adjusted (sex, age, BMI, smoking status, low-density lipoprotein cholesterol, systolic blood pressure, and fasting blood glucose) means for the IMT measurements were lowest in the Arg109 and Arg223 homozygotes (P=0.042 and P=0.041, ANCOVA, respectively).


CONCLUSIONS
The variations in the LEPR gene are independently associated with early atherosclerosis and some of its risk factors. These variations could possibly affect leptin signaling and thereby modify the effects of leptin on the atherosclerotic process.
Saukko
Meiju
M
Institute of Clinical Medicine, Department of Internal Medicine and Biocenter Oulu, University of Oulu and Clinical Research Center, Oulu University Hospital, Oulu, Finland.
Kesäniemi
Y Antero
YA
Ukkola
Olavi
O
D017667:Adipocytes / Q000166:cytology; D001120:Arginine / Q000737:chemistry*; D050197:Atherosclerosis / Q000097:blood* / Q000235:genetics; D001794:Blood Pressure; D015992:Body Mass Index; D042783:Endothelial Cells / Q000166:cytology; D005260:Female; D005973:Glutamine / Q000737:chemistry*; D006801:Humans; D020738:Leptin / Q000097:blood; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D011110:Polymorphism, Genetic; D011897:Random Allocation; D054411:Receptors, Leptin / Q000737:chemistry*; D012307:Risk Factors
D020738:Leptin; D054411:Receptors, Leptin; D005973:Glutamine; D001120:Arginine