Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Association of K121Q polymorphism in ENPP1 (PC-1) with BMI in Caucasian and African-American adults

International Journal of Obesity volume 30, pages 233–237 (2006)Cite this article

Abstract

Objective:

To test for association of the ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) K121Q polymorphism with body mass index (BMI) and diabetes in a large sample of Caucasians and African-Americans by selectively genotyping individuals at the extremes of the phenotypic distribution.

Subjects:

Subsets comprising the extremes of the BMI distribution (10th–20th and above the 90th BMI percentile for Caucasians and between the 10th–30th and above the 80th percentile for African-Americans) from a group of 10 260 Caucasian and 2268 African-American adults participating in New York Cancer Project were studied.

Methods:

Subjects were genotyped for the ENPP1 K121Q polymorphism by pyrosequencing and tested for association with BMI and diabetes by regression analysis.

Results:

Regression analysis with BMI as the dependent variable demonstrated a significant association (P=0.02) of genotype at K121Q with BMI, with no significant race-by-genotype interaction (P=0.30). Compared with Q/Q or Q/K individuals, the K/K individuals had a BMI approximately 1.3 kg/m2 higher, without effects of age, gender or race. By logistic regression analysis, the K121Q alleles had no significant effect on diabetes status (P=0.37) in obese subjects.

Conclusion:

In both Caucasians and African-Americans, the K121 polymorphism in ENPP1 was associated with increased BMI, but not with diabetes.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. van Driel IR, Goding JW . Plasma cell membrane glycoprotein PC-1: primary structure deduced from cDNA clones. J Biol Chem 1987; 262: 4882–4887.

    CAS  PubMed  Google Scholar 

  2. Harahap AR, Goding JW . Distribution of the murine plasma cell antigen PC-1 in non-lymphoid tissues. J Immunol 1988; 141: 2317–2320.

    CAS  PubMed  Google Scholar 

  3. Maddux BA, Goldfine ID . Membrane glycoprotein PC-1 inhibition of insulin receptor function occurs via direct interaction with the receptor α-subunit. Diabetes 2000; 49: 13–19.

    Article  CAS  Google Scholar 

  4. Costanzo BV, Trischitta V, Di Paola R, Spampinato D, Pizzuti A, Vigneri R et al. The Q allele variant (Gln121) of membrane glycoprotein PC-1 interacts with the insulin receptor and inhibits insulin signaling more effectively than the common K allele variant (Lys121). Diabetes 2001; 50: 831–836.

    Article  CAS  Google Scholar 

  5. Pizzuti A, Frittitta L, Argiolas A, Baratta R, Goldfine ID, Bozzali M et al. A polymorphism (K121Q) of the human glycoprotein PC-1 gene coding region is strongly associated with insulin resistance. Diabetes 1999; 48: 1881–1884.

    Article  CAS  Google Scholar 

  6. Frittitta L, Baratta R, Spampinato D, Di Paola R, Pizzuti A, Vigneri R et al. The Q121 PC-1 variant and obesity have additive and independent effects in causing insulin resistance. J Clin Endocrinol Metab 2001; 86: 5888–5891.

    Article  CAS  Google Scholar 

  7. Kubaszek A, Pihlajamäki J, Karhapää P, Vauhkonen I, Laakso M . The K121Q polymorphism of the PC-1 gene is associated with insulin resistance but not with dyslipidemia. Diabetes Care 2003; 26: 464–467.

    Article  CAS  Google Scholar 

  8. Gu HF, Almgren P, Lindholm E, Frittitta L, Pizzuti A, Trischitta V et al. Association between the human glycoprotein PC-1 gene and elevated glucose and insulin levels in a paired-sibling analysis. Diabetes 2000; 49: 1601–1603.

    Article  CAS  Google Scholar 

  9. Hamaguchi K, Terao H, Kusuda Y, Yamashita T, Hazoury Bahles JA, Cruz LLM et al. The PC-1 Q121 allele is exceptionally prevalent in the Dominican Republic and is associated with type 2 diabetes. J Clin Endocrinol Metab 2004; 89: 1359–1364.

    Article  CAS  Google Scholar 

  10. Rasmussen SK, Urhammer SA, Pizzuti A, Echwald SM, Ekstrøm CT, Hansen L et al. The K121Q variant of the human PC-1 gene is not associated with insulin resistance or type 2 diabetes among Danish Caucasians. Diabetes 2000; 49: 1608–1611.

    Article  CAS  Google Scholar 

  11. González-Sánchez JL, Martínez-Larrad MT, Fernández-Pérez C, Kubaszek A, Laakso M, Serrano-Ríos M . K121Q PC-1 gene polymorphism is not associated with insulin resistance in a Spanish population. Obes Res 2003; 11: 603–605.

    Article  Google Scholar 

  12. Meyre D, Lecoeur C, Vatin V, Mouton S, Weill J, Froguel P . Genetic and phenotypic evidence for an obesity and insulin resistance on locus 6q16–q23 in French obese children. Diabetes 2003; 52 (Suppl 1): A26–A27 (abstract #115-OR).

    Google Scholar 

  13. Jenkinson CP, Richardson DK, Rodriguez L, Schneider J, Streng P, Arya R et al. Comprehensive analysis of SNPs in ENPP1: association with diabesity. Am J Hum Genet 2004; 75 (Suppl 1): 45 (abstract #137).

    Google Scholar 

  14. DeCosmo S, Argiolas A, Miscio G, Thomas S, Piras GP, Trevisan R et al. A PC-1 amino acid variant (K121Q) is associated with faster progression of renal disease in patients with type 1 diabetes and albuminuria. Diabetes 2000; 49: 521–524.

    Article  CAS  Google Scholar 

  15. Canani LH, Ng DPK, Smiles A, Rogus JJ, Warram JH, Krolewski AS . Polymorphism in ecto-nucleotide pyrophosphatase/phosphodiesterase 1 gene (ENPP1/PC1) and early development of advanced diabetic nephropathy in type 1 diabetes. Diabetes 2002; 51: 1188–1193.

    Article  CAS  Google Scholar 

  16. Endler G, Mannhalter C, Sunder-Plassmann H, Schillinger M, Klimersch A, Exner M et al. The K121Q polymorphism in the plasma cell membrane glycoprotein 1 gene predisposes to early myocardial infarction. J Mol Med 2002; 80: 791–795.

    Article  CAS  Google Scholar 

  17. Rutsch F, Vaingankar S, Johnson K, Goldfine I, Maddux B, Schauerte P et al. PC-1 nucleoside triphosphate pyrophosphohydrolase deficiency in idiopathic infantile arterial calcification. Am J Pathol 2001; 158: 543–554.

    Article  CAS  Google Scholar 

  18. Rutsch F, Ruf N, Vaingankar S, Toliat MR, Suk A, Höhne W et al. Mutations in ENPP1 are associated with ‘idiopathic’ infantile arterial calcification. Nat Genet 2003; 34: 379–381.

    Article  CAS  Google Scholar 

  19. Mitchell MK, Gregersen PK, Johnson S, Parsons R, Vlahov D . The New York Cancer Project: rationale, organization, design, and baseline characteristics. J Urban Health 2004; 81: 301–310.

    Article  Google Scholar 

  20. Quade D . Rank analysis of covariance. J Am Stat Assoc 1967; 62: 1187–1200.

    Article  Google Scholar 

  21. Atwood LD, Heard-Costa NL, Cupples LA, Jaquish CE, Wilson PWF, D'Agostino RB . Genomewide linkage analysis of body mass index across 28 years of the Framingham Heart Study. Am J Hum Genet 2002; 71: 1044–1050.

    Article  CAS  Google Scholar 

  22. Duggirala R, Blangero J, Almasy L, Arya R, Dyer TD, Williams KL et al. A major locus for fasting insulin concentrations and insulin resistance on chromosome 6q with strong pleiotropic effects on obesity-related phenotypes in nondiabetic Mexican Americans. Am J Hum Genet 2001; 68: 1149–1164.

    Article  CAS  Google Scholar 

  23. Meyre D, Lecoeur C, Delplanque J, Francke S, Vatin V, Durand E et al. A genome-wide scan for childhood obesity-associated traits in French families shows significant linkage on chromosome 6q22.31–q23.2. Diabetes 2004; 53: 803–811.

    Article  CAS  Google Scholar 

  24. Jacobsen BK, Bønaa KH, Njølstad I . Cardiovascular risk factors, change in risk factors over 7 years, and the risk of clinical diabetes mellitus type 2: The Tromsø study. J Clin Epidemiol 2002; 55: 647–653.

    Article  Google Scholar 

Download references

Acknowledgements

This study was supported by grants NIDDK 52431 and 56336, an American Diabetes Association mentored fellowship and support provided by the Academic Medicine Development Corporation (AMDeC) of New York. Naoki Matsuoka is also supported by Uehara Memorial Foundation and Foundation for Growth Science, Tokyo, Japan. We thank Robert Lundsten, Frank Fries, and Rebecca Yohannes for technical assistance and Ana Ignat, Lizzett Santiago, and Richard Sarver for assistance with manuscript preparation.

Author information

Authors and Affiliations

  1. Division of Molecular Genetics, Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, NY, USA

    N Matsuoka, R L Leibel & W K Chung

  2. Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA

    A Patki, H K Tiwari & D B Allison

  3. Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA

    H K Tiwari

  4. Department of Public Health & Clinical Nutrition Research Center, University of Alabama at Birmingham, Birmingham, AL, USA

    D B Allison

  5. Department of Biomedical Informatics, College of Physicians and Surgeons, Columbia University, New York, NY, USA

    S B Johnson

  6. The Robert S Boas Center for Genomics and Human Genetics, The North Shore-Long Island Jewish Research Institute, Manhasset, NY, USA

    P K Gregersen

  7. Department of Medicine, Naomi Berrie Diabetes Center, College of Physicians and Surgeons, Columbia University, New York, NY, USA

    R L Leibel & W K Chung

Authors
  1. N Matsuoka
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A Patki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H K Tiwari
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D B Allison
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S B Johnson
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. P K Gregersen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. R L Leibel
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. W K Chung
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to W K Chung.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Matsuoka, N., Patki, A., Tiwari, H. et al. Association of K121Q polymorphism in ENPP1 (PC-1) with BMI in Caucasian and African-American adults. Int J Obes 30, 233–237 (2006). https://doi.org/10.1038/sj.ijo.0803132

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijo.0803132

Keywords

This article is cited by

Search

Advanced search

Quick links