Skip to main content
SpringerLink
Log in

No conclusive evidence for association of polymorphisms in the adiponectin receptor 1 gene, AdipoR1, with common obesity

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

AdipoR1 is one of the adiponectin receptors which are important for adiponectin signaling. Because adiponectin is a candidate gene for common obesity, it is also hypothesized that variations in AdipoR1 may be involved in the development of complex obesity. Therefore, we designed an association study for the AdipoR1 gene. We performed a case–control association study including 1,021 obese subjects (mean age 42 ± 12 years; mean BMI 38.2 ± 6.2 kg/m²) and 226 lean, healthy individuals (mean age 36 ± 7 years; mean BMI 22.1 ± 1.7 kg/m²). Nine tagSNPs were selected to cover the entire AdipoR1 gene and surrounding 7 kb region (based on HapMap data). TagSNPs were genotyped using AcycloPrime-Fluorescence Polarization (FP) SNP Detection kits and TaqMan Pre-Designed SNP Genotyping assays according to manufacturer’s protocols. We found that the rs1075399 non-reference allele decreases obesity risk by 45 % in men only [odds ratio (OR) = 0.55, 95 % CI 0.35–0.87, nominal P = 0.010]. However, after Bonferroni correction for multiple testing, this association is lost. None of the other tagSNPs were associated with obesity when studying the entire population, nor when looking at men and women separately. Quantitative analysis of the effect of each SNP on height, weight, and BMI revealed that none of the tagSNPs are associated with weight or BMI. We report here that we found no decisive evidence for association between AdipoR1 tagSNPs and complex obesity in our Belgian Caucasian population.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. WHO: Fact Sheet N311. www.who.int (2011). Accessed 26 Mar 2012

  2. P.G. Kopelman, Obesity as a medical problem. Nature 404(6778), 635–643 (2000)

    PubMed  CAS  Google Scholar 

  3. L.F. Van Gaal, I.L. Mertens, C.E. De Block, Mechanisms linking obesity with cardiovascular disease. Nature 444(7121), 875–880 (2006)

    Article  PubMed  Google Scholar 

  4. N. Bouatia-Naji, D. Meyre, S. Lobbens, K. Seron, F. Fumeron, B. Balkau, B. Heude, B. Jouret, P.E. Scherer, C. Dina, J. Weill, P. Froguel, ACDC/adiponectin polymorphisms are associated with severe childhood and adult obesity. Diabetes 55(2), 545–550 (2006)

    Article  PubMed  CAS  Google Scholar 

  5. R.J. Loos, S. Ruchat, T. Rankinen, A. Tremblay, L. Perusse, C. Bouchard, Adiponectin and adiponectin receptor gene variants in relation to resting metabolic rate, respiratory quotient, and adiposity-related phenotypes in the Quebec family study. Am. J. Clin. Nutr. 85(1), 26–34 (2007)

    PubMed  CAS  Google Scholar 

  6. S. Beckers, A.V. Peeters, F. de Freitas, I.L. Mertens, S.L. Verhulst, D. Haentjens, K.N. Desager, L.F. Van Gaal, W. Van Hul, Association study and mutation analysis of adiponectin shows association of variants in APM1 with complex obesity in women. Ann. Hum. Genet. 73(Pt 5), 492–501 (2009)

    Article  PubMed  CAS  Google Scholar 

  7. W. Du, Q. Li, Y. Lu, X. Yu, X. Ye, Y. Gao, J. Ma, J. Cheng, Y. Cao, J. Du, H. Shi, L. Zhou, Genetic variants in ADIPOQ gene and the risk of type 2 diabetes: a case–control study of Chinese Han population. Endocrine 40(3), 413–422 (2011)

    Article  PubMed  CAS  Google Scholar 

  8. H. Jia, L. Yu, X. Guo, W. Gao, Z. Jiang, Associations of adiponectin gene polymorphisms with polycystic ovary syndrome: a meta-analysis. Endocrine (2012). doi:10.1007/s12020-012-9605-3

  9. T. Yamauchi, J. Kamon, Y. Ito, A. Tsuchida, T. Yokomizo, S. Kita, T. Sugiyama, M. Miyagishi, K. Hara, M. Tsunoda, K. Murakami, T. Ohteki, S. Uchida, S. Takekawa, H. Waki, N.H. Tsuno, Y. Shibata, Y. Terauchi, P. Froguel, K. Tobe, S. Koyasu, K. Taira, T. Kitamura, T. Shimizu, R. Nagai, T. Kadowaki, Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 423(6941), 762–769 (2003)

    Article  PubMed  CAS  Google Scholar 

  10. A. Coope, M. Milanski, E.P. Araujo, M. Tambascia, M.J. Saad, B. Geloneze, L.A. Velloso, AdipoR1 mediates the anorexigenic and insulin/leptin-like actions of adiponectin in the hypothalamus. FEBS Lett. 582(10), 1471–1476 (2008)

    Article  PubMed  CAS  Google Scholar 

  11. M. Bjursell, A. Ahnmark, Y.M. Bohlooly, L. William-Olsson, M. Rhedin, X.R. Peng, K. Ploj, A.K. Gerdin, G. Arnerup, A. Elmgren, A.L. Berg, J. Oscarsson, D. Linden, Opposing effects of adiponectin receptors 1 and 2 on energy metabolism. Diabetes 56(3), 583–593 (2007)

    Article  PubMed  CAS  Google Scholar 

  12. S.A. Miller, D.D. Dykes, H.F. Polesky, A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 16(3), 1215 (1988)

    Article  PubMed  CAS  Google Scholar 

  13. P.I. de Bakker, R. Yelensky, I. Pe’er, S.B. Gabriel, M.J. Daly, D. Altshuler, Efficiency and power in genetic association studies. Nat. Genet. 37(11), 1217–1223 (2005)

    Article  PubMed  Google Scholar 

  14. J. Ott, Documentation to LINKAGE UTILITY programs. http://linkage.rockefeller.edu/ott/linkutil.htm (2005). Accessed 16 May 2011

  15. W.J. Gauderman, J.M. Morrison, QUANTO 1.1: A computer program for power and sample size calculations for genetic-epidemiology studies. http://hydra.usc.edu/gxe (2006). Accessed 19 Apr 2011

  16. C.M. Damcott, S.H. Ott, T.I. Pollin, L.J. Reinhart, J. Wang, J.R. O’Connel, B.D. Mitchell, A.R. Shuldiner, Genetic variation in adiponectin receptor 1 and adiponectin receptor 2 is associated with type 2 diabetes in the Old Order Amish. Diabetes 54(7), 2245–2250 (2005)

    Article  PubMed  CAS  Google Scholar 

  17. N. Stefan, F. Machicao, H. Staiger, J. Machann, F. Schick, O. Tschritter, C. Spieth, C. Weigert, A. Fritsche, M. Stumvoll, H.U. Haring, Polymorphisms in the gene encoding adiponectin receptor 1 are associated with insulin resistance and high liver fat. Diabetologia 48(11), 2282–2291 (2005)

    Article  PubMed  CAS  Google Scholar 

  18. S.C. Collins, J. Luan, A.J. Thompson, A. Daly, R.K. Semple, S. O’Rahilly, N.J. Wareham, I. Barroso, Adiponectin receptor genes: mutation screening in syndromes of insulin resistance and association studies for type 2 diabetes and metabolic traits in UK populations. Diabetologia 50(3), 555–562 (2007)

    Article  PubMed  CAS  Google Scholar 

  19. L. Qi, A. Doria, E. Giorgi, F.B. Hu, Variations in adiponectin receptor genes and susceptibility to type 2 diabetes in women: a tagging-single nucleotide polymorphism haplotype analysis. Diabetes 56(6), 1586–1591 (2007)

    Article  PubMed  CAS  Google Scholar 

  20. E. Yeh, L. Kimura, F.I. Errera, C.B. Angeli, R.C. Mingroni-Netto, M.E. Silva, L.H. Canani, M.R. Passos-Bueno, Association of polymorphisms at the ADIPOR1 regulatory region with type 2 diabetes and body mass index in a Brazilian population with European or African ancestry. Braz. J. Med. Biol. Res. (Revista brasileira de pesquisas medicas e biologicas/Sociedade Brasileira de Biofisica et al.) 41(6), 468–472 (2008)

    Google Scholar 

  21. T.L. Edwards, D.R. Velez Edwards, R. Villegas, S.S. Cohen, M.S. Buchowski, J.H. Fowke, D. Schlundt, J.R. Long, Q. Cai, W. Zheng, X.O. Shu, M.K. Hargreaves, S. Jeffrey, S.M. Williams, L.B. Signorello, W.J. Blot, C.E. Matthews, HTR1B, ADIPOR1, PPARGC1A, and CYP19A1 and obesity in a cohort of Caucasians and African Americans: an evaluation of gene–environment interactions and candidate genes. Am. J. Epidemiol. 175(1), 11–21 (2012)

    Article  PubMed  Google Scholar 

  22. S.S. Cohen, M.D. Gammon, K.E. North, R.C. Millikan, E.M. Lange, S.M. Williams, W. Zheng, Q. Cai, J. Long, J.R. Smith, L.B. Signorello, W.J. Blot, C.E. Matthews, ADIPOQ, ADIPOR1, and ADIPOR2 polymorphisms in relation to serum adiponectin levels and BMI in black and white women. Obesity 19(10), 2053–2062 (2011)

    Article  PubMed  CAS  Google Scholar 

  23. N. Siitonen, L. Pulkkinen, U. Mager, J. Lindstrom, J.G. Eriksson, T.T. Valle, H. Hamalainen, P. Ilanne-Parikka, S. Keinanen-Kiukaanniemi, J. Tuomilehto, M. Laakso, M. Uusitupa, Association of sequence variations in the gene encoding adiponectin receptor 1 (ADIPOR1) with body size and insulin levels. The Finnish Diabetes Prevention Study. Diabetologia 49(8), 1795–1805 (2006)

    Article  PubMed  CAS  Google Scholar 

  24. D.K. Richardson, J. Schneider, M.J. Fourcaudot, L.M. Rodriguez, R. Arya, T.D. Dyer, L. Almasy, J. Blangero, M.P. Stern, R.A. Defronzo, R. Duggirala, C.P. Jenkinson, Association between variants in the genes for adiponectin and its receptors with insulin resistance syndrome (IRS)-related phenotypes in Mexican Americans. Diabetologia 49(10), 2317–2328 (2006)

    Article  PubMed  CAS  Google Scholar 

  25. The 1000 Genomes Project Consortium, A map of human genome variation from population-scale sequencing. Nature 467(7319), 1061–1073 (2010)

    Google Scholar 

  26. Exome Variant Server, NHLBI Exome Sequencing Project (ESP). http://evs.gs.washington.edu/EVS/ (2012). Accessed 19 June 2012

Download references

Acknowledgments

This study was supported by a grant from the Research Foundation-Flanders (FWO Vlaanderen) to LVG and WVH. SB is a postdoctoral fellow of the Research Foundation-Flanders (FWO Vlaanderen). DZ holds a predoctoral specialization scholarship from the Agency for Innovation by Science and Technology in Flanders (IWT).

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Medical Genetics, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium

    S. Beckers, F. de Freitas, D. Zegers, J. K. Van Camp & W. Van Hul

  2. Department of Endocrinology, Diabetology and Metabolic Diseases, Antwerp University Hospital, Wilrijkstraat 10, 2650, Antwerp, Belgium

    I. L. Mertens, A. Verrijken & L. F. Van Gaal

Authors
  1. S. Beckers
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F. de Freitas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D. Zegers
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. I. L. Mertens
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. Verrijken
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J. K. Van Camp
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. L. F. Van Gaal
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. W. Van Hul
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to W. Van Hul.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Beckers, S., de Freitas, F., Zegers, D. et al. No conclusive evidence for association of polymorphisms in the adiponectin receptor 1 gene, AdipoR1, with common obesity. Endocrine 43, 120–126 (2013). https://doi.org/10.1007/s12020-012-9736-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-012-9736-6

Keywords

Search

Navigation