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 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 HighWire Citing Articles via Google Scholar Google Scholar Articles by Lyon, H. N. Articles by Hirschhorn, J. N. Search for Related Content PubMed PubMed Citation Articles by Lyon, H. N. Articles by Hirschhorn, J. N. Social Bookmarking                What's this?

Common Variants in the ENPP1 Gene Are Not Reproducibly Associated With Diabetes or Obesity

¹ Divisions of Genetics and Endocrinology, Program in Genomics, Children’s Hospital, Boston, Massachusetts
² Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts
³ Department of Pediatrics, Harvard Medical School, Boston, Massachusetts
⁴ Department of Medicine, Harvard Medical School, Boston, Massachusetts
⁵ Center for Human Genetic Research, Massachusets General Hospital, Boston, Massachusetts
⁶ Department of Medicine, Massachusetts General Hospital; Boston, Massachusetts
⁷ Department of Endocrinology, University Hospital MAS, Lund University, Malmö, Sweden
⁸ Department of Clinical Science, University Hospital MAS, Lund University, Malmö, Sweden
⁹ Department of Medicine, Helsinki University Central Hospital and Research Program for Molecular Medicine, University of Helsinki, Helsinki, Finland
¹⁰ Folkhälsan Research Center, Helsinki, Finland
¹¹ Community Genomic Medicine Center, Montreal University and Lipid Clinic, Chicoutimi Hospital, Quebec, Canada
¹² Department of Preventive Medicine and Epidemiology, Loyola University Medical Center, Maywood, Illinois
¹³ Genomics Collaborative Division, SeraCare LifeSciences, Cambridge, Massachusetts
¹⁴ Department of Genetics, Harvard Medical School, Boston, Massachusetts

Address correspondence and reprint requests to Joel N. Hirschhorn, Division of Genetics, Children’s Hospital Boston, Enders 561, 300 Longwood Ave., Boston, MA 02115. E-mail: joelh{at}broad.mit.edu

Abbreviations: SNP, single nucleotide polymorphism

The common missense single nucleotide polymorphism (SNP) K121Q in the ectoenzyme nucleotide pyrophosphate phosphodiesterase (ENPP1) gene has recently been associated with type 2 diabetes in Italian, U.S., and South-Asian populations. A three-SNP haplotype, including K121Q, has also been associated with obesity and type 2 diabetes in French and Austrian populations. We set out to confirm these findings in several large samples. We genotyped the haplotype K121Q (rs1044498), rs1799774, and rs7754561 in 8,676 individuals of European ancestry with and without type 2 diabetes, in 1,900 obese and 930 lean individuals of European ancestry from the U.S. and Poland, and in 1,101 African-American individuals. Neither the K121Q missense polymorphism nor the putative risk haplotype were significantly associated with type 2 diabetes or BMI. Two SNPs showed suggestive evidence of association in a meta-analysis of our European ancestry samples. These SNPs were rs7754561 with type 2 diabetes (odds ratio for the G-allele, 0.85 [95% CI 0.78–0.92], P = 0.00003) and rs1799774 with BMI (homozygotes of the delT-allele, 0.6 [0.42–0.88], P = 0.007). However, these findings are not supported by other studies. We did not observe a reproducible association between these three ENPP1 variants and BMI or type 2 diabetes.

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

This article has been cited by other articles:

				E. S. Stolerman, A. K. Manning, J. B. McAteer, J. Dupuis, C. S. Fox, L. A. Cupples, J. B. Meigs, and J. C. Florez Haplotype Structure of the ENPP1 Gene and Nominal Association of the K121Q Missense Single Nucleotide Polymorphism With Glycemic Traits in the Framingham Heart Study Diabetes, July 1, 2008; 57(7): 1971 - 1977. [Abstract] [Full Text] [PDF]

				J. B. McAteer, S. Prudente, S. Bacci, H. N. Lyon, J. N. Hirschhorn, V. Trischitta, J. C. Florez, and for the ENPP1 Consortium The ENPP1 K121Q Polymorphism Is Associated With Type 2 Diabetes in European Populations: Evidence From an Updated Meta-Analysis in 42,042 Subjects Diabetes, April 1, 2008; 57(4): 1125 - 1130. [Abstract] [Full Text] [PDF]

				K. L. Keene, J. C. Mychaleckyj, S. G. Smith, T. S. Leak, P. S. Perlegas, C. D. Langefeld, B. I. Freedman, S. S. Rich, D. W. Bowden, and M. M. Sale Association of the Distal Region of the Ectonucleotide Pyrophosphatase/Phosphodiesterase 1 Gene With Type 2 Diabetes in an African-American Population Enriched for Nephropathy Diabetes, April 1, 2008; 57(4): 1057 - 1062. [Abstract] [Full Text] [PDF]

				C. H. Andreasen, K. L. Stender-Petersen, M. S. Mogensen, S. S. Torekov, L. Wegner, G. Andersen, A. L. Nielsen, A. Albrechtsen, K. Borch-Johnsen, S. S. Rasmussen, et al. Low Physical Activity Accentuates the Effect of the FTO rs9939609 Polymorphism on Body Fat Accumulation Diabetes, January 1, 2008; 57(1): 95 - 101. [Abstract] [Full Text] [PDF]

				P. Eller, K. Hochegger, G. M. Feuchtner, E. Zitt, I. Tancevski, A. Ritsch, F. Kronenberg, A. R. Rosenkranz, J. R. Patsch, and G. Mayer Impact of ENPP1 genotype on arterial calcification in patients with end-stage renal failure Nephrol. Dial. Transplant., September 10, 2007; (2007) gfm566v1. [Abstract] [Full Text] [PDF]

				M. N. Weedon, B. Shields, G. Hitman, M. Walker, M. I. McCarthy, A. T. Hattersley, and T. M. Frayling No Evidence of Association of ENPP1 Variants With Type 2 Diabetes or Obesity in a Study of 8,089 U.K. Caucasians Diabetes, November 1, 2006; 55(11): 3175 - 3179. [Abstract] [Full Text] [PDF]