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

  1. Swneke D. Bailey1,
  2. J C. Loredo-Osti2,
  3. Pierre Lepage3,
  4. Janet Faith3,
  5. Joelle Fontaine3,
  6. Katia M. Desbiens4,
  7. Thomas J. Hudson1345,
  8. Claude Bouchard6,
  9. Daniel Gaudet7,
  10. Louis Pérusse89,
  11. Marie-Claude Vohl910 and
  12. James C. Engert145
  1. 1Department of Human Genetics, McGill University, Montréal, Québec, Canada
  2. 2Department of Mathematic and Statistics, Memorial University of Newfoundland, St. John’s, Newfoundland, Canada
  3. 3McGill University and Genome Québec Innovation Centre, Montréal, Québec, Canada
  4. 4Research Institute of the McGill University Health Centre, Montréal, Québec, Canada
  5. 5Department of Medicine, McGill University, Montréal, Québec, Canada
  6. 6Pennington Biomedical Research Centre, Baton Rouge, Louisiana
  7. 7Dyslipidemia, Diabetes and Atherosclerosis Group and Community Genomics Research Center, Université de Montréal and Chicoutimi Hospital, Québec, Canada
  8. 8Department of Social and Preventive Medicine, Division of Kinesiology, Laval University, Québec, Canada
  9. 9Lipid Research Center, Laval University Hospital Research Center, Québec, Canada
  10. 10Department of Food Science and Nutrition, Laval University, Québec, Canada
  1. 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

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

Footnotes

  • Additional information for this article can be found in an online appendix at http://diabetes.diabetesjournals.org.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted June 27, 2006.
    • Received February 9, 2006.
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This Article

  1. doi: 10.2337/db06-0189 Diabetes October 2006 vol. 55 no. 10 2896-2902
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  2. Full Text
  3. Full Text (PDF)
  4. Online-Only Appendix

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