Molecular screening of the ghrelin gene in Italian obese children: the Leu72Met variant is associated with an earlier onset of obesity.
OBJECTIVE
To test whether ghrelin variants could play a role in modulating some aspects of the obese phenotype during childhood.


METHODS
We screened the ghrelin gene in 300 Italian obese children and adolescents (mean age 10.5+/-3.2 y; range 4-19 y) and 200 controls by using the single-strand conformation polymorphism and the restriction fragment length polymoprhism analysis.


RESULTS
No mutations were detected with the exception of two previously described polymorphisms, Arg51Gln and Leu72Met. For both variations, allelic frequencies were similar between patients and controls. Interestingly, we showed that the Leu72Met polymorphism was associated with differences in the age at obesity onset. Patients with the Met72 allele became obese earlier than homozygous patients for the wild Leu72 allele. The logrank test comparing the plots of the complement of Kaplan-Meier estimates between the two groups of patients was statistically significant (P<0.0001).


CONCLUSIONS
It is unlikely that ghrelin variations cause the obesity due to single-gene mutations. The Leu72Met polymorphism of the ghrelin gene seems to play a role in anticipating the onset of obesity among children suggesting, therefore, that ghrelin may be involved in the pathophysiology of human adiposity.
Miraglia del Giudice
E
E
Department of Pediatrics, Second University of Napoli, Napoli, Italy. emanuele.miraglia@unina2.it
Santoro
N
N
Cirillo
G
G
Raimondo
P
P
Grandone
A
A
D'Aniello
A
A
Di Nardo
M
M
Perrone
L
L
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D015992:Body Mass Index; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D014644:Genetic Variation; D005838:Genotype; D054439:Ghrelin; D006801:Humans; D008297:Male; D009765:Obesity / Q000235:genetics*; D036361:Peptide Hormones / Q000235:genetics*; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D016016:Proportional Hazards Models
D054439:Ghrelin; D036361:Peptide Hormones