| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on March 9, 2006
Accepted on September 5, 2006
Medical Department III, University of Leipzig, Leipzig, Germany; University Hospital for Children and Adolescents, University of Leipzig, Leipzig, Germany; Vestische Hospital for Children and Adolescents Datteln, University of Witten/Herdecke, Datteln, Germany
* To whom correspondence should be addressed. E-mail: peter.kovacs{at}medizin.uni-leipzig.de.
Context: ENPP1 (nucleotide pyrophosphatase/phosphodiesterase-1) encodes a membrane-bound glycoprotein that inhibits the insulin-receptor tyrosine kinase activity, resulting in reduced insulin sensitivity. Hence, variants in this gene may be related to obesity and insulin resistance.
Objective: In this study, we therefore aimed to explore the role of ENPP1 genetic variants in obesity and related traits in a representative population of Caucasian children and in cohorts of obese children with detailed metabolic characteristics including oral glucose tolerance test.
Design: We genotyped the K121Q, IVS20delT-11 and A/G+1044TGA ENPP1 genetic variants for association analyses in 712 schoolchildren (346 boys and 366 girls; mean age 12 ± 3 yr; mean BMI-SDS (SD-score) 0.09 ± 0.04) and in independent cohorts of 205 obese children from Leipzig and 195 obese children from Datteln, Germany.
Results: We identified a significantly increased risk of obesity in Leipzig children carrying the 121Q variant (adjusted OR: 1.82, 95%CI 1.30-2.56, P = 0.0005) or the [Q-delT-G] haplotype (and 1.75 (1.17-2.62), P = 0.006) as compared with a lean control group. This was replicated in another independent obesity/overweight cohort from Leipzig as well as obese children from Datteln. In addition, obese children from Leipzig with the [Q-delT-G] haplotype were characterized by impaired glucose metabolism, while the [K-delT-G] and [K-insT-A] haplotypes were significantly associated with improved insulin sensitivity and glucose metabolism (all P < 0.05 after adjusting for age, gender and BMI).
Conclusions: In conclusion, our study suggests a potential role of the K121Q polymorphism or derived ENPP1 haplotypes in increased susceptibility to obesity and early impairment of glucose and insulin metabolism in children.
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]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 I. D. Goldfine, B. A. Maddux, J. F. Youngren, G. Reaven, D. Accili, V. Trischitta, R. Vigneri, and L. Frittitta The Role of Membrane Glycoprotein Plasma Cell Antigen 1/Ectonucleotide Pyrophosphatase Phosphodiesterase 1 in the Pathogenesis of Insulin Resistance and Related Abnormalities Endocr. Rev., February 1, 2008; 29(1): 62 - 75. [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., January 1, 2008; 23(1): 321 - 327. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Stutzmann, V. Vatin, S. Cauchi, A. Morandi, B. Jouret, O. Landt, P. Tounian, C. Levy-Marchal, R. Buzzetti, L. Pinelli, et al. Non-synonymous polymorphisms in melanocortin-4 receptor protect against obesity: the two facets of a Janus obesity gene Hum. Mol. Genet., August 1, 2007; 16(15): 1837 - 1844. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Prudente and V. Trischitta The Pleiotropic Effect of the ENPP1 (PC-1) Gene on Insulin Resistance, Obesity, and Type 2 Diabetes J. Clin. Endocrinol. Metab., December 1, 2006; 91(12): 4767 - 4768. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
