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Common Polymorphisms in the Promoter of the Visfatin Gene (PBEF1) Influence Plasma Insulin Levels in a French-Canadian Population

¹ Department of Human Genetics, McGill University, Montréal, Québec, Canada
² Department of Mathematic and Statistics, Memorial University of Newfoundland, St. John’s, Newfoundland, Canada
³ McGill University and Genome Québec Innovation Centre, Montréal, Québec, Canada
⁴ Research Institute of the McGill University Health Centre, Montréal, Québec, Canada
⁵ Department of Medicine, McGill University, Montréal, Québec, Canada
⁶ Pennington Biomedical Research Centre, Baton Rouge, Louisiana
⁷ Dyslipidemia, Diabetes and Atherosclerosis Group and Community Genomics Research Center, Université de Montréal and Chicoutimi Hospital, Québec, Canada
⁸ Department of Social and Preventive Medicine, Division of Kinesiology, Laval University, Québec, Canada
⁹ Lipid Research Center, Laval University Hospital Research Center, Québec, Canada
¹⁰ Department of Food Science and Nutrition, Laval University, Québec, Canada

Address correspondence and reprint requests to Dr. James C. Engert, McGill University, Division of Cardiology, Royal Victoria Hospital, H7.11, 687 Pine Ave. West, Montréal, Québec, Canada H3A 1A1. E-mail: jamie.engert{at}mcgill.ca

Abbreviations: apoB, apolipoprotein B; CHD, coronary heart disease; Coup-TF, chick ovalbumin upstream promoter–transcription factor; DR, direct repeat; HRE, hormone response element; LD, linkage disequilibrium; PPAR, peroxisome poliferator–activated receptor; SNP, single nucleotide polymorphism; QFS, Quebec Family Study

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 0.02). In addition, a more distal SNP (rs7789066) was significantly associated with the apolipoprotein B component of VLDL (P = 0.012).

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