title: Common polymorphisms in the promoter of the visfatin gene (PBEF1) influence plasma insulin levels in a French-Canadian population.
abstract: The adipokine visfatin (PBEF1) exhibits insulin-mimetic effects and correlates strongly with visceral adiposity. We sequenced visfatin gene exons and 1,480 bp of the promoter in 23 individuals, including 18 individuals from the Quebec Family Study (QFS) with varying degrees of abdominal visceral fat, assessed by computed tomography, and 5 individuals from the Saguenay-Lac-Saint-Jean region of Québec. We identified a synonymous polymorphism in exon 7 (SER301SER) but no nonsynonymous mutations. We observed an additional 10 polymorphisms, including 5 intronic, 4 within the promoter, and 1 within the 3' untranslated region. Further promoter sequencing (816 bp) identified five additional single nucleotide polymorphisms (SNPs) in the QFS population. To investigate the role of visfatin gene variants in obesity-related phenotypes, we genotyped a total of 13 SNPs in the promoter region of the gene. From these, we analyzed the seven common SNPs in the QFS sample (918 participants from 208 families). A significant association was found between two SNPs (rs9770242 and rs1319501), in perfect linkage disequilibrium, and fasting insulin levels (P = 0.002). These SNPs were also associated with fasting glucose (P <or= 0.02). In addition, a more distal SNP (rs7789066) was significantly associated with the apolipoprotein B component of VLDL (P = 0.012).
authors.affiliation: Department of Human Genetics, McGill University, Montréal, Québec, Canada H3A 1A1.
authors.forename: Swneke D
authors.initials: SD
authors.lastname: Bailey
authors.forename: J C
authors.initials: JC
authors.lastname: Loredo-Osti
authors.forename: Pierre
authors.initials: P
authors.lastname: Lepage
authors.forename: Janet
authors.initials: J
authors.lastname: Faith
authors.forename: Joelle
authors.initials: J
authors.lastname: Fontaine
authors.forename: Katia M
authors.initials: KM
authors.lastname: Desbiens
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hudson
authors.forename: Claude
authors.initials: C
authors.lastname: Bouchard
authors.forename: Daniel
authors.initials: D
authors.lastname: Gaudet
authors.forename: Louis
authors.initials: L
authors.lastname: Pérusse
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Vohl
authors.forename: James C
authors.initials: JC
authors.lastname: Engert
mesh_terms: D000328:Adult; D016207:Cytokines / Q000235:genetics*; D005260:Female; D018703:Founder Effect; D005602:France / Q000208:ethnology; D006801:Humans; D007328:Insulin / Q000097:blood*; D015810:Linkage Disequilibrium; D008297:Male; D054409:Nicotinamide Phosphoribosyltransferase; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011792:Quebec
chemical_list: D016207:Cytokines; D007328:Insulin; D054409:Nicotinamide Phosphoribosyltransferase; C085455:nicotinamide phosphoribosyltransferase, human