title: Bardet-Biedl syndrome gene variants are associated with both childhood and adult common obesity in French Caucasians.
abstract: Bardet-Biedl syndrome (BBS) is a rare developmental disorder with the cardinal features of abdominal obesity, retinopathy, polydactyly, cognitive impairment, renal and cardiac anomalies, hypertension, and diabetes. BBS is genetically heterogeneous, with nine genes identified to date and evidence for additional loci. In this study, we performed mutation analysis of the coding and conserved regions of BBS1, BBS2, BBS4, and BBS6 in 48 French Caucasian individuals. Among the 36 variants identified, 12 were selected and genotyped in 1,943 French-Caucasian case subjects and 1,299 French-Caucasian nonobese nondiabetic control subjects. Variants in BBS2, BBS4, and BBS6 showed evidence of association with common obesity in an age-dependent manner, the BBS2 single nucleotide polymorphism (SNP) being associated with common adult obesity (P = 0.0005) and the BBS4 and BBS6 SNPs being associated with common early-onset childhood obesity (P = 0.0003) and common adult morbid obesity (0.0003 < P < 0.007). The association of the BBS4 rs7178130 variant was found to be supported by transmission disequilibrium testing (P = 0.006). The BBS6 variants also showed nominal evidence of association with quantitative components of the metabolic syndrome (e.g., dyslipidemia, hyperglycemia), a complication previously described in BBS patients. In summary, our preliminary data suggest that variations at BBS genes are associated with risk of common obesity.
authors.affiliation: Section of Genomic Medicine, Faculty of Medicine, Imperial College, Hammersmith Hospital, Du Cane Road, London, W12 0NN, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Benzinou
authors.forename: Andrew
authors.initials: A
authors.lastname: Walley
authors.forename: Stephan
authors.initials: S
authors.lastname: Lobbens
authors.forename: Marie-Aline
authors.initials: MA
authors.lastname: Charles
authors.forename: Béatrice
authors.initials: B
authors.lastname: Jouret
authors.forename: Frédéric
authors.initials: F
authors.lastname: Fumeron
authors.forename: Beverley
authors.initials: B
authors.lastname: Balkau
authors.forename: David
authors.initials: D
authors.lastname: Meyre
authors.forename: Philippe
authors.initials: P
authors.lastname: Froguel
mesh_terms: D000328:Adult; D020788:Bardet-Biedl Syndrome / Q000235:genetics*; D002648:Child; D005602:France; D056385:Group II Chaperonins; D006801:Humans; D008869:Microtubule-Associated Proteins; D018832:Molecular Chaperones / Q000235:genetics; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D044465:White People
chemical_list: C429655:BBS4 protein, human; C464790:Bbs1 protein, human; C473309:Bbs2 protein, human; C414726:MKKS protein, human; D008869:Microtubule-Associated Proteins; D018832:Molecular Chaperones; D011506:Proteins; D056385:Group II Chaperonins