Background: 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. Aims: 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/m(2)) diagnosed before the age of 30 years. Methods: 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. Results: Three sequence variations were detected: -422T>C in the 5'-UTR region, and -8007>A (rs10418248) and -8606>T in the promoter region. The SNPs -422 T>C in the 5'-UTR region and -8606>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 -8606>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 -8606>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). Conclusion: 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.
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