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:

Linkage analysis of circulating levels of adiponectin in hispanic children

Abstract

Introduction:

Adiponectin, a hormone produced exclusively by adipose tissue, is inversely associated with insulin resistance and proinflammatory conditions. The aim of this study was to find quantitative trait loci (QTLs) that affect circulating levels of adiponectin in Hispanic children participating in the VIVA LA FAMILIA Study by use of a systematic genome scan.

Methods:

The present study included extended families with at least one overweight child between 4 and 19 years old. Overweight was defined as body mass index (BMI) 95th percentile. Fasting blood was collected from 466 children from 127 families. Adiponectin was assayed by radioimmunoassay (RIA) technique in fasting serum. A genome-wide scan on circulating levels of adiponectin as a quantitative phenotype was conducted using the variance decomposition approach.

Results:

The highest logarithm of odds (LOD) score (4.2) was found on chromosome 11q23.2–11q24.2, and a second significant signal (LOD score=3.0) was found on chromosome 8q12.1–8q21.3. In addition, a signal suggestive of linkage (LOD score=2.5) was found between 18q21.3 and 18q22.3. After adjustment for BMI-Z score, the LOD score on chromosome 11 remained unchanged, but the signals on chromosomes 8 and 18 dropped to 1.6 and 1.7, respectively. Two other signals suggestive of linkage were found on chromosome 3 (LOD score=2.1) and 10 (LOD score=2.5). Although the region on chromosome 11 has been associated with obesity and diabetes-related traits in adult populations, this is the first observation of linkage in this region for adiponectin levels. Our suggestive linkages on chromosomes 10 and 3 replicate results for adiponectin seen in other populations. The influence of loci on chromosomes 18 and 8 on circulating adiponectin seemed to be mediated by BMI in the present study.

Conclusion:

Our genome scan in children has identified a novel QTL and replicated QTLs in chromosomal regions previously shown to be linked with obesity and type 2 diabetes (T2D)-related phenotypes in adults. The genetic contribution of loci to adiponectin levels may vary across different populations and age groups. The strong linkage signal on chromosome 11 is most likely underlain by a gene(s) that may contribute to the high susceptibility of these Hispanic children to obesity and T2D.

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

Access options

Buy this article

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

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Kershaw E, Flier J . Adipose tissue as an endocrine organ. J Clin Endocrinol Metabol 2004; 89: 2548–2556.

    Article  CAS  Google Scholar 

  2. Esposito K, Pontillo A, Di Palo C, Giugliano G, Masella M, Marfella R et al. Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial. JAMA 2003; 289: 1799–1804.

    Article  CAS  Google Scholar 

  3. Hotta K, Funahashi T, Bodkin NL, Ortmeyer HK, Arita Y, Hansen BC et al. Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity during the progression to type 2 diabetes in rhesus monkeys. Diabetes 2001; 50: 1126–1133.

    Article  CAS  Google Scholar 

  4. Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J et al. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun 1999; 257: 79–83.

    Article  CAS  Google Scholar 

  5. Bacha F, Saad R, Gungor N, Arslanian S . Adiponectin in youth. Relationship to visceral adiposity, insulin sensitivity and β-cell function. Diabetes Care 2004; 27: 547–552.

    Article  CAS  Google Scholar 

  6. Reinehr T, Roth C, Menke T, Adler W . Adiponectin before and after weight loss in obese children. J Clin Endocrinol Metab 2004; 89: 3790–3794.

    Article  CAS  Google Scholar 

  7. Butte NF, Comuzzie AG, Cai G, Cole SA, Mehta NR, Bacino CA et al. Genetic and environmental factors influencing fasting serum adiponectin in Hispanic children. J Clin Endocrinol Metabol 2005; In press.

  8. Perusse L, Rankinen T, Zuberi A, Chagnon YC, Weisnagel SJ, Argyropoulos G et al. The human obesity gene map: the 2004 map. Obes Res 2005; 13: 381–490.

    Article  CAS  Google Scholar 

  9. Kissebah AH, Sonnenberg GE, Myklebust J, Goldstein M, Broman K, James RG et al. Quantitative trait loci on chromosomes 3 and 17 influence phenotypes of the metabolic syndrome. Proc Natl Acad Sci USA 2000; 97: 14478–14483.

    Article  CAS  Google Scholar 

  10. Vasseur F, Lepretre F, Lacquemant C, Froguel P . Single nucleotide polymorphism haplotypes in the both proximal promoter and exon 3 of the AMP1 gene modulate adipocyte-secreted adiponectin hormone levels and contribute to the genetic risk for type 2 diabetes in French Caucasians. Hum Mol Genet 2002; 11: 2607–2614.

    Article  CAS  Google Scholar 

  11. Comuzzie AG, Funahashi T, Sonnenberg G, Martin LJ, Jacob HJ, Black AE et al. The genetic basis of plasma variation in adiponectin, a global endophenotype for obesity and the metabolic syndrome. J Clin Endocrinol Metab 2001; 86: 4321–4325.

    Article  CAS  Google Scholar 

  12. Pollin TI, Tanner K, O’connell JR, Ott SH, Damcott CM, Shuldiner AR et al. Linkage of plasma adiponectin levels to 3q27 explained by association with variation in the APM1 gene. Diabetes 2005; 54: 268–274.

    Article  CAS  Google Scholar 

  13. Lindsay RS, Funahashi T, Krakoff J, Matsuzawa Y, Tanaka S, Kobes S et al. Genome-wide linkage analysis of serum adiponectin in the Pima Indian Population. Diabetes 2003; 52: 2419–2425.

    Article  CAS  Google Scholar 

  14. Chuang LM, Chiu YF, Sheu WH, Hung YJ, Ho LT, Grove J et al. Biethnic comparisons of autosomal genomic scan for loci linked to plasma adiponectin in populations of Chinese and Japanese origin. J Clin Endocrinol Metab 2005; 89: 5772–5778.

    Article  Google Scholar 

  15. Dib C, Faure S, Fizames C, Samson D, Drouot N, Vignal A et al. A comprehensive genetic map of the human genome based on 5,264 microsatellites. Nature 1996; 380: 152–154.

    Article  CAS  Google Scholar 

  16. Sun L, Wilder K, McPeek MS . Enhanced pedigree error detection. Hum Hered 2002; 54: 99–110.

    Article  Google Scholar 

  17. Sobel E, Papp JC, Lange K . Detection and integration of genotyping errors in statistical genetics. Am J Hum Genet 2002; 70: 496–508.

    Article  Google Scholar 

  18. Heath SM . Markov chain Monte Carlo segregation and linkage analysis for oligogenic models. Am J Hum Genet 1997; 61: 748–760.

    Article  CAS  Google Scholar 

  19. Hopper JL, Mathews JD . Extensions to multivariate normal models for pedigree analysis. Am J Hum Genet 1982; 46: 373–383.

    Article  CAS  Google Scholar 

  20. Blangero J, Williams JT, Almasy L . Robust LOD scores for variance component-based linkage analysis. Genet Epidemiol 2000; 29: S8–S14.

    Article  Google Scholar 

  21. Butte NF, Comuzzie AG, Cole SA, Mehta NR, Tejero ME, Bastarrachea R et al. Quantitative genetic analysis of the metabolic syndrome in hispanic children. Ped Res 2005; 58: 1243–1248.

    Article  CAS  Google Scholar 

  22. Ogden CL, Flegal KM, Carroll MD, Johnson CL . Prevalence and trends in overweight among US children and adolescents, 1999–2000. JAMA 2002; 288: 1728–1732.

    Article  Google Scholar 

  23. Stein CM, Song Y, Elston RC, Jun G, Tiwari HK, Iyengar SK . Structural equation model-based genome scan for the metabolic syndrome. BMC Genet 2003; 4: S99–S103.

    Article  Google Scholar 

  24. Imperatore G, Knowler WC, Kobes S, Bennett PH, Hanson RL . Genome-wide linkage analysis of factors characterizing the metabolic syndrome among Pima Indians [abstract]. Diabetes 1999; 48 (Suppl): A182.

    Google Scholar 

  25. Ghosh S, Watanabe RM, Valle TT, Hauser ER, Magnuson VL, Langefeld CD et al. The Finland–United States investigation of non-insulin-dependent diabetes mellitus genetics (fusion) study. II An autosomal genome scan for genes that predispose to type 2 diabetes. Am J Human Genet 2000; 67: 1174–1185.

    CAS  Google Scholar 

  26. Watanabe RM, Ghosh S, Langefeld CD, Valle TT, Hauser ER, Magnuson VL et al. The Finland–United States investigation of non-insulin-dependent diabetes mellitus genetics (fusion) study. II An autosomal genome scan for diabetes-related quantitative trait loci. Am J Human Genet 2000; 67: 1186–1200.

    CAS  Google Scholar 

  27. Van Tilburg JH, Sandkuijl LA, Stengman EM, Pearson PL, van Haeften TW, Wijmenga C . Variance component analysis of obesity in type 2 diabetes confirms loci on chromosomes 1q and 11q. Obes Res 2003; 11: 1290–1294.

    Article  CAS  Google Scholar 

  28. Baier L, Kovacs P, Wiedrich C, Cray K, Schemidt A, Shen GQ et al. Positional cloning of an obesity/diabetes susceptibility gene(s) on chromosome 11 in Pima Indians. Ann NY Acad Sci 2002; 967: 258–264.

    Article  CAS  Google Scholar 

  29. Jenkinson CP, Hanson R, Cray K, Wiedrich C, Knowler WC, Bogardus C et al. Association of dopamine D2 receptor polymorphisms Ser311Cys and TaqIA with obesity or type 2 diabetes mellitus in Pima Indians. Int J Obes Relat Metab Disord 2000; 24: 1233–1238.

    Article  CAS  Google Scholar 

  30. Katoh M, Katoh M . IGSF11 gene, frequently up-regulated in intestinal-type gastric cancer, encodes adhesion molecule homologous to CXADR, FLJ22415 and ESAM. Int J Oncol 2003; 23: 525–531.

    CAS  PubMed  Google Scholar 

  31. Massague J . TGF-beta signal transduction. Annu Rev Biochem 1998; 67: 753–791.

    Article  CAS  Google Scholar 

  32. Hirata K, Ishida T, Penta K, Rezaee M, Yang E Wohlgemuth J, Quertermous T . Cloning of an immunoglobulin family adhesion molecule selectively expressed by endothelial cells. J Biol Chem 2001; 276: 16223–16231.

    Article  CAS  Google Scholar 

  33. Kang JS, Mulieri PJ, Hu Y, Taliana L, Krauss RS . BOC, an Ig superfamily member, associates with CDO to positively regulate myogenic differentiation. EMBO J 2002; 21: 114–124.

    Article  CAS  Google Scholar 

  34. Yamamoto M, Sato S, Hemmi H, Sanjo H, Uematsu S, Kaisho T et al. Essential role for TIRAP in activation of the signaling cascade shared by TLR2 and TLR4. Nature 2002; 420: 324–329.

    Article  CAS  Google Scholar 

  35. Lopes CM, Zhang H, Rohacs T, Jin T, Yang J, Logothetis DE . Alterations in conserved Kir channel-PIP2 interactions underlie channelopathies. Neuron 2002; 34: 933–944.

    Article  CAS  Google Scholar 

  36. Turner S, Kardia S, Boerwincle E de AM . Multivariate linkage analysis of blood pressure and body mass index. Genet Epidemiol 2004; 27: 64–73.

    Article  Google Scholar 

  37. Li W, Dong C, Li D, Zhao H, Price R . An obesity-related locus in chromosome region 12q23–24. Diabetes 2004; 53: 812–820.

    Article  CAS  Google Scholar 

  38. Saar K, Geller F, Ruschendorf F, Reis A, Friedel S, Schauble N et al. Genome scan for childhood and adolescent obesity in German families. Pediatrics 2003; 111: 321–327.

    Article  Google Scholar 

  39. Stone S, Abkevich V, Hunt SC, Gutin A, Russell DL, Neff CD et al. A major predisposition to locus for severe obesity, at 4p15–p14. Am J Hum Genet 2002; 70: 1459–1468.

    Article  CAS  Google Scholar 

  40. Comuzzie AG, Hixson JE, Almasy L, Mitchell BD, Mahaney MC, Dyer TD et al. A major quantitative trait locus determining serum leptin levels and fat mass is located on human chromosome 2. Nat Genet 1997; 15: 273–276.

    Article  CAS  Google Scholar 

  41. Frayling TM, Lindgren CM, Chevre JC, Menzel S, Wishart M, Benmezroua Y et al. Young-onset type 2 diabetes families are the major contributors to genetic loci in the diabetes UK Warren 2 genome scan and identify putative novel loci on chromosomes 8q21, 21q22 and 22q11. Diabetes 2003; 52: 1857–1863.

    Article  CAS  Google Scholar 

  42. Ohman M, Oksanen L, Kaprio J, Koskenvuo M, Mustajoki P, Rissanen A et al. Genome-wide scan of obesity Finnish sibpairs reveals linkage to chromosome Xq24. J Clin Endocrinol Metab 2000; 85: 3183–3190.

    CAS  Google Scholar 

  43. Chagnon YC, Chen WJ, Perusse L, Chagnon M, Nadeau A, Wilkison WO et al. Linkage and association studies between the melanocortin receptors 4 and 5 genes and obesity-related phenotypes in the Quebec family study. Mol Med 1997; 3: 663–673.

    Article  CAS  Google Scholar 

  44. Li WD, Dong C, Li D, Garrigan C, Price RA . A quantitative trait locus influencing fasting plasma glucose in chromosome region 18q22–23. Diabetes 2004; 53: 2487–2491.

    Article  CAS  Google Scholar 

  45. Norman RA, Thompson DB, Foroud T, Garvey WT, Bennett PH, Bogardus C et al. Genome wide search for genes influencing percent body fat in Pima Indians: suggestive linkage at chromosome 11q21–q22. Pima diabetes gene group. Am J Hum Genet 1997; 60: 166–173.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Adeyemo A, Luke A, Cooper R, Wu X, Tayo B, Zhu X et al. A genome-wide scan for body mass index among Nigerian families. Obes Res 2003; 11: 266–273.

    Article  Google Scholar 

  47. Platte P, Papanicolaou GJ, Johnston J, Klein CM, Doheny KF, Pugh EW et al. A study of linkage and association of body mass index in the Old Order Amish. Am J Med Genet 2003; 121C: 71–80.

    Article  CAS  Google Scholar 

  48. Norman RA, Tataranni PA, Pratley R, Thompson DB, Hanson RL, Prochazka M et al. Autosomal genomic scan for loci linked to obesity and energy metabolism in Pima Indians. Am J Hum Genet 1998; 62: 659–668.

    Article  CAS  Google Scholar 

  49. Hsueh WC, Mitchel B, Schneider J, St Jean P, Pollin TI, Ehm MG et al. Genome-wide scan of obesity in the Old order. Amish J Clin Endocrinol Metab 2001; 86: 1199–1205.

    CAS  PubMed  Google Scholar 

  50. Lindsay RS, Kobes S, Knowler WC, Bennett PH, Hanson RL . Genome-wide linkage analysis assessing parent-of-origin effects in the inheritance of type 2 diabetes and BMI in Pima Indians. Diabetes 2001; 50: 2850–2857.

    Article  CAS  Google Scholar 

  51. Arya R, Duggirala R, Jenkinson CP, Almasy L, Blangero J, O’Connell P et al. Evidence of a novel quantitative-trait locus for obesity on chromosome 4p in Mexican–Americans. Am J Hum Genet 2004; 74: 272–282.

    Article  CAS  Google Scholar 

  52. Dong C, Wang S, Li W, Li D, Zhao H, Price R . Interacting genetic loci on chromosomes 20 and 10 influence extreme obesity in humans. Am J Hum Genet 2003; 72: 115–124.

    Article  CAS  Google Scholar 

  53. Price RA, Li WD, Bernstein A, Crystal A, Golding EM, Weisberg SJ et al. A locus affecting obesity in human chromosome region 10p12. Diabetologia 2001; 44: 363–366.

    Article  CAS  Google Scholar 

  54. Hager J, Dina C, Francke S, Dubois S, Houari M, Vatin V et al. A genome-wide scan for human obesity genes reveals a major susceptibility locus on chromosome 10. Nat Genet 1998; 20: 304–308.

    Article  CAS  Google Scholar 

  55. Hinney A, Ziegler A, Oeffner F, Wedewardt C, Vogel M, Wulftange H et al. Independent confirmation of a major locus for obesity on chromosome 10. J Clin Endocrinol Metab 2000; 85: 2962–2965.

    Article  CAS  Google Scholar 

  56. Palmer LJ, Buxbaum SG, Larkin EK, Patel SR, Elston RC, Tishler PV et al. Whole genome scan for obstructive sleep apnea and obesity in African–American families. Am J Respir Crit Care Med 2004; 169: 1314–1321.

    Article  Google Scholar 

  57. Mitchell B, Cole SA, Comuzzie AG, Almasy L, Blangero J, MacCluer JW et al. A quantitative trait locus influencing BMI maps to the region of the beta-3 adrenergic receptor. Diabetes 1999; 48: 1863–1867.

    Article  CAS  Google Scholar 

  58. Gorlova O, Amos C, Wang N, Shete S, Turner S, Boerwinkle E . Genetic linkage and imprinting effects on body mass index in children and young adults. Eur J Hum Genet 2003; 11: 425–432.

    Article  CAS  Google Scholar 

  59. Chagnon YC, Rice T, Perusse L, Borecki IB, Ho-Kim MA, Lacaille M et al. HERITAGE family study. Genomic scan for genes affecting body composition before and after training in Caucasians from HERITAGE. J Appl Physiol 2001; 90: 1777–1787.

    Article  CAS  Google Scholar 

  60. Li W, Dong C, Li D, Zhao H, Price R . An obesity-related locus on chromosome region 12q23–24. Diabetes 2004; 53: 812–820.

    Article  CAS  Google Scholar 

  61. North KE, Rose KM, Borecki IB, Oberman A, Hunt SC, Miller MB et al. Evidence for a gene on chromosome 13 influencing postural systolic blood pressure change and body mass index. Hypertension 2004; 43: 780–784.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank the families who participated in this study, and to acknowledge the contributions of Mercedes Alejandro and Marilyn Navarrete for study coordination, and Sopar Seributra for nursing and Theresa Wilson, Tina Ziba, Maurice Puyau, Firoz Vohra, Anne Adolph, Roman Shypailo, JoAnn Pratt and Maryse Laurent for technical assistance, Grace Meixner and Daniel Zamarripa for genotyping and Jennifer Darling for the data analysis. This work is a publication of the US Department of Agriculture (USDA)/Agricultural Research Service (ARS) Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, USA. This project was funded with federal funds from the NIH R01 DK59264 and from USDA/ARS under Cooperative Agreement 58-6250-51000-037. The contents of this publication do not necessarily reflect the views or policies of the USDA, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to A G Comuzzie.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tejero, M., Cai, G., Göring, H. et al. Linkage analysis of circulating levels of adiponectin in hispanic children. Int J Obes 31, 535–542 (2007). https://doi.org/10.1038/sj.ijo.0803436

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijo.0803436

Keywords

This article is cited by

Search

Quick links