Polymorphism in Leptin and Leptin Receptor Genes May Modify Leptin Levels and Represent Risk Factors for Multiple Sclerosis.
BACKGROUND
Leptin, the product of the ob gene, can modulate the immune responses and also seems to regulate Th1/Th2 balance by promoting a shift from the Th2 to the Th1 inflammatory cytokine pathway. Therefore, in this study, we aimed to investigate the association between polymorphisms of leptin gene (LEP) and leptin receptor gene (LEPR) and susceptibility to multiple sclerosis (MS). In addition, we investigated the influence of these two common polymorphisms on plasma levels of leptin.


METHODS
This case-control study was conducted on 232 MS patients and 204 control subjects. Serum level measurement of leptin was performed using enzyme-linked immunosorbent assay (ELISA). G-2548-A LEP polymorphism and 223A/G polymorphism of the LEPR were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).


RESULTS
There was a significant difference in allele/genotype frequencies of LEP gene among MS patients and control subjects (p<0.01). The genotype frequencies of LEPR polymorphism were also significantly different between control subjects and MS patients (p=0.02). The mean serum level of leptin was significantly higher in MS patients as compared with the controls (p<0.01).


CONCLUSIONS
Our study implicates a significant role of LEP and LEPR polymorphisms and also leptin levels in the risk of MS and its severity. Furthermore, our findings suggest LEP and LEPR polymorphisms as important predictors for increased serum leptin in Iranian MS patients. Although this study provides new clinically relevant information regarding genetic determinants modulating risk of MS, further investigations are necessary to understand better the mechanistic implications of these observations in the development of MS.
a Department of Neurology , School of Medicine, Isfahan University of Medical Sciences , Isfahan , Iran.
Mehrdad
M
Farrokhi
a Department of Neurology , School of Medicine, Isfahan University of Medical Sciences , Isfahan , Iran.
Mehrnoosh
M
Dabirzadeh
b Faculty of Medicine , Islamic Azad University of Najafabad , Najafabad , Isfahan , Iran.
Elyas
E
Fadaee
a Department of Neurology , School of Medicine, Isfahan University of Medical Sciences , Isfahan , Iran.
Ali Amani
AA
Beni
c Department of Radiology , School of Medicine, Isfahan University of Medical Sciences , Isfahan , Iran.
Zahra
Z
Saadatpour
d Department of Radiology , School of Medicine, Najafabad University of Medical Sciences , Isfahan , Iran.
Ali
A
Rezaei
e Department of Pharmacology and Toxicology , School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences , Isfahan , Iran.
Zahra
Z
Heidari
D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007492:Iran; D020738:Leptin / Q000235:genetics*; D008297:Male; D009103:Multiple Sclerosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D054411:Receptors, Leptin / Q000235:genetics*; D012307:Risk Factors; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*
C515448:LEPR protein, human; D020738:Leptin; D054411:Receptors, Leptin
ELISA; leptin; leptin receptor; multiple sclerosis; polymerase chain reaction; polymorphism