Common polymorphisms in the promoter of the visfatin gene (PBEF1) influence plasma insulin levels in a French-Canadian population.
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).
Bailey
Swneke D
SD
Department of Human Genetics, McGill University, Montréal, Québec, Canada H3A 1A1.
Loredo-Osti
J C
JC
Lepage
Pierre
P
Faith
Janet
J
Fontaine
Joelle
J
Desbiens
Katia M
KM
Hudson
Thomas J
TJ
Bouchard
Claude
C
Gaudet
Daniel
D
Pérusse
Louis
L
Vohl
Marie-Claude
MC
Engert
James C
JC
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
D016207:Cytokines; D007328:Insulin; D054409:Nicotinamide Phosphoribosyltransferase; C085455:nicotinamide phosphoribosyltransferase, human