HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Online-Only Appendix All Versions of this Article: db06-1051v1 56/5/1460    most recent Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Campbell, C. D. Articles by Hirschhorn, J. N. Search for Related Content PubMed PubMed Citation Articles by Campbell, C. D. Articles by Hirschhorn, J. N. Social Bookmarking                What's this?

Association Studies of BMI and Type 2 Diabetes in the Neuropeptide Y Pathway

A Possible Role for NPY2R as a Candidate Gene for Type 2 Diabetes in Men

¹ Program in Genomics and Division of Endocrinology, Children's Hospital, Boston, Massachusetts
² Department of Genetics, Harvard Medical School, Boston, Massachusetts
³ Program in Medical and Population Genetics, Broad Institute of the Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts
⁴ Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland
⁵ Folkhalsan Genetic Institute, Folkhalsan Research Center, and the Research Program for Molecular Medicine, University of Helsinki, Helsinki, Finland
⁶ University of Montreal Community Genomic Center, Chicoutimi Hospital, Quebec, Canada
⁷ Department of Preventive Medicine and Epidemiology, Loyola University Medical Center, Maywood, Illinois
⁸ Genomics Collaborative/Seracare LifeSciences, Cambridge, Massachusetts
⁹ Department of Clinical Sciences, Diabetes, and Endocrinology, University Hospital, Lund University, Malmö, Sweden

Address correspondence and reprint requests to Joel N. Hirschhorn, Enders 561, Children's Hospital, 300 Longwood Avenue, Boston, MA 021115. E-mail: joelh{at}broad.mit.edu

Abbreviations: CEPH, Centre d'Etude du Polymorphisme Humain; FHS, Framingham Heart Study; NHLBI, National Heart, Lung, and Blood Institute; NPY, neuropeptide Y; PYY, polypeptide YY; SNP, single nucleotide polymorphism

The neuropeptide Y (NPY) family of peptides and receptors regulate food intake. Inherited variation in this pathway could influence susceptibility to obesity and its complications, including type 2 diabetes. We genotyped a set of 71 single nucleotide polymorphisms (SNPs) that capture the most common variation in NPY, PPY, PYY, NPY1R, NPY2R, and NPY5R in 2,800 individuals of recent European ancestry drawn from the near extremes of BMI distribution. Five SNPs located upstream of NPY2R were nominally associated with BMI in men (P values = 0.001–0.009, odds ratios [ORs] 1.27–1.34). No association with BMI was observed in women, and no consistent associations were observed for other genes in this pathway. We attempted to replicate the association with BMI in 2,500 men and tested these SNPs for association with type 2 diabetes in 8,000 samples. We observed association with BMI in men in only one replication sample and saw no association in the combined replication samples (P = 0.154, OR = 1.09). Finally, a 9% haplotype was associated with type 2 diabetes in men (P = 1.73 x 10^–4, OR = 1.36) and not in women. Variation in this pathway likely does not have a major influence on BMI, although small effects cannot be ruled out; NPY2R should be considered a candidate gene for type 2 diabetes in men.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?