title: Identification of sequence variants in the UBL5 (ubiquitin-like 5 or BEACON) gene in obese children by PCR-SSCP: no evidence for association with obesity.
abstract: Childhood obesity has a strong genetic background. The human UBL5 (BEACON) gene has been suggested as a candidate gene for obesity. Previous studies in populations of different ethnicities have shown a significant association between UBL5 variants and measures of body fatness.
  
  
  
  To identify mutations that may cause early-onset obesity we screened the UBL5 gene for sequence variations in a cohort of obese children who also had at least one obese parent (BMI >30 kg/m2) diagnosed before the age of 30 years.
  
  
  
  We screened the UBL5 gene by PCR-SSCP and sequencing in a cohort (n=30) of obese children (mean age 6.9 +/- 3 yr), and then analysed SNPs by HRMA in a population of 160 obese and 140 lean individuals.
  
  
  
  Three sequence variations were detected: -422T>C in the 5'-UTR region, and -800T>A (rs10418248) and -860G>T in the promoter region. The SNPs -422 T>C in the 5'-UTR region and -860G>T have never been described before. These two SNPs did not co-segregate with obesity in relatives of the obese carriers. However, since in silico analysis of the -860G>T SNP region predicted a loss of the consensus binding site for RXR-alpha and RXR-beta, both involved in adipose cell regulation, we screened the -860G>T variant in a cohort of 300 individuals, 160 young obese (mean age 33 years) and 140 lean individuals. No differences in genotype distribution or in -860T allele frequencies were found between the two groups (1.8% vs. 1.4%, p = NS). In addition, no association was found between obesity and the previously described -800T>A SNP (rs10418248).
  
  
  
  Our data suggest that the UBL5 gene is unlikely to play a major role in the genetic susceptibility to early-onset obesity in our population.
authors.affiliation: Department of Medical Sciences, Endocrinology and Metabolism, University of Cagliari, Cagliari, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Sentinelli
authors.forename: Stefano
authors.initials: S
authors.lastname: Romeo
authors.forename: Valentina M
authors.initials: VM
authors.lastname: Cambuli
authors.forename: Efisio
authors.initials: E
authors.lastname: Cossu
authors.forename: Maria Gisella
authors.initials: MG
authors.lastname: Cavallo
authors.forename: Sara
authors.initials: S
authors.lastname: Zavarella
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Spoletini
authors.forename: Raffaella
authors.initials: R
authors.lastname: Buzzetti
authors.forename: Marco Giorgio
authors.initials: MG
authors.lastname: Baroni
mesh_terms: D000328:Adult; D017668:Age of Onset; D001835:Body Weight / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000208:ethnology / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D014452:Ubiquitins / Q000235:genetics*
chemical_list: D005136:Eye Proteins; C429294:UBL5 protein, human; D014452:Ubiquitins