title: Analysis of the SIM1 contribution to polygenic obesity in the French population.
abstract: SIM1 (single-minded 1) haploinsufficiency is responsible for obesity in both humans and mice, but the contribution of frequent DNA variation to polygenic obesity is unknown. Sequencing of all exons, exon/intron boundaries, 870 base pairs (bp) of the putative promoter, and 1,095 bp of the 3'UTR of SIM1 gene in 143 obese children and 24 control adults identified 13 common variants. After analysis of the linkage disequilibrium (LD) structure, association study of eight variants was performed in 1,275 obese children and severely obese adults, in 1,395 control subjects, and in 578 obesity-selected pedigrees. A nominal evidence of association was found for the nonsynonymous variant P352T C/A (rs3734354) (P = 0.01, OR = 0.81 (0.70-0.95)), the +2,004 TGA -/insT SNP (rs35180395) (P = 0.02, OR = 1.21 (1.02-1.43)), the +2,215A/G TGA SNP (rs9386126) (P = 0.002, OR = 0.81 (0.71-0.93)), and pooled childhood/adult obesity. Even though transmission disequilibrium test (TDT) further supported the association of P352T and +2,004 -/inst T with obesity, none of these nominal associations remained significant after a multiple testing Bonferroni correction. Therefore, our study excludes a major contribution of SIM1 common variants in exons, 5' and 3' UTR regions in polygenic obesity susceptibility in French Europeans.
authors.affiliation: Genomics and Molecular Physiology of Metabolic Diseases, CNRS 8090-Institute of Biology, Pasteur Institute, Lille, France.
authors.forename: Maya
authors.initials: M
authors.lastname: Ghoussaini
authors.forename: Fanny
authors.initials: F
authors.lastname: Stutzmann
authors.forename: Cyril
authors.initials: C
authors.lastname: Couturier
authors.forename: Vincent
authors.initials: V
authors.lastname: Vatin
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Durand
authors.forename: Cécile
authors.initials: C
authors.lastname: Lecoeur
authors.forename: Franck
authors.initials: F
authors.lastname: Degraeve
authors.forename: Barbara
authors.initials: B
authors.lastname: Heude
authors.forename: Maithé
authors.initials: M
authors.lastname: Tauber
authors.forename: Serge
authors.initials: S
authors.lastname: Hercberg
authors.forename: Claire
authors.initials: C
authors.lastname: Levy-Marchal
authors.forename: Patrick
authors.initials: P
authors.lastname: Tounian
authors.forename: Jacques
authors.initials: J
authors.lastname: Weill
authors.forename: Michael
authors.initials: M
authors.lastname: Traurig
authors.forename: Clifton
authors.initials: C
authors.lastname: Bogardus
authors.forename: Leslie J
authors.initials: LJ
authors.lastname: Baier
authors.forename: Jacques L
authors.initials: JL
authors.lastname: Michaud
authors.forename: Philippe
authors.initials: P
authors.lastname: Froguel
authors.forename: David
authors.initials: D
authors.lastname: Meyre
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D002648:Child; D005602:France; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D008875:Middle Aged; D020412:Multifactorial Inheritance; D009765:Obesity / Q000235:genetics*; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D012097:Repressor Proteins / Q000235:genetics*; D044465:White People / Q000235:genetics*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D012097:Repressor Proteins; C491094:SIM1 protein, human