Diabetes
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Appendix
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Connie Hung, C.-C.
Right arrow Articles by Farooqi, I. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Connie Hung, C.-C.
Right arrow Articles by Farooqi, I. S.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Diabetes 53:2461-2466, 2004
© 2004 by the American Diabetes Association, Inc.

Studies of the Peptide YY and Neuropeptide Y2 Receptor Genes in Relation to Human Obesity and Obesity-Related Traits

Chiao-Chien Connie Hung1, Fraser Pirie2, Jian’an Luan3, Emma Lank1, Ayesha Motala2, Giles S.H. Yeo1, Julia M. Keogh1, Nicholas J. Wareham3, Stephen O’Rahilly1, and I. Sadaf Farooqi1

1 University Departments of Medicine and Clinical Biochemistry, Cambridge Institute for Medical Research, Cambridge, U.K
2 Endocrine/Diabetes Unit, Nelson R. Mandela School of Medicine, University of Natal, Natal, South Africa
3 Department of Public Health and Epidemiology, Addenbrookes’ Hospital, Cambridge, U.K

Peptide-YY (PYY) is secreted from endocrine L-cells of the gastrointestinal tract in response to caloric ingestion and may mediate postprandial satiety through the hypothalamic neuropeptide Y2 receptor (Y2R). We examined whether variants in the genes encoding PYY and Y2R might be associated with obesity-related phenotypes in humans. Among 101 subjects with severe early-onset obesity and a history of hyperphagia, we found two rare sequence variants—L73P and IVS2 + 32delG—in PYY and three rare missense mutations—L40F, F87I, and A172T—in Y2R. Although none of these were found in 100 normal-weight white control subjects, L73P in PYY and F87I and A172T in Y2R did not segregate with obesity in family studies, and family data were unavailable for IVS2 + 32delG in PYY and L40F in Y2R. Two common single nucleotide polymorphisms (SNPs), R72T and IVS3 + 68C>T, in PYY were in tight linkage disequilibrium but showed no association with BMI in a large white population. In the Y2R, two SNPs, 585T>C and 936T>C, were found and were in tight linkage disequilibrium. Men, homozygous for the rarer variant, had significantly lower BMI (P = 0.017), waist-to-hip ratio (P = 0.013), and, surprisingly, higher nonesterified fatty acid levels (P = 0.01). In conclusion, mutations in PYY and Y2R are not commonly found in humans with severe early-onset obesity. The relationship between common variants in Y2R and obesity-related traits deserves further exploration in other populations.

Address correspondence and reprint requests to Stephen O’Rahilly or I. Sadaf Farooqi, University Department of Clinical Biochemistry, Addenbrookes’ Hospital, Cambridge, CB2 2QQ, U.K. E-mail: sorahill{at}hgmp.mrc.ac.uk or ifarooqi{at}hgmp.mrc.ac.uk

Address correspondence and reprint requests to Stephen O’Rahilly or I. Sadaf Farooqi, University Department of Clinical Biochemistry, Addenbrookes’ Hospital, Cambridge, CB2 2QQ, U.K. E-mail: sorahill{at}hgmp.mrc.ac.uk or ifarooqi{at}hgmp.mrc.ac.uk


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




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2004 by the American Diabetes Association.