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.

  • Pediatric Highlight
  • Published:

Candidate genes and growth curves for adiposity in African- and European-American youth

Abstract

Objective:

Obesity is associated with multiple health problems and often originates in childhood. This study investigated the association of genes with the development of general and central obesity from childhood into adulthood.

Design:

Individual growth curves for measures of general adiposity were examined in an 11-year (1987–1998) cohort study. Single-nucleotide polymorphisms (SNPs) in 11 candidate genes were genotyped.

Subjects:

Five hundred and twenty-six subjects classified by race (49% African American (AA)), sex (47% male) and socio-economic status (SES).

Results:

AA female carriers of the 27Glu allele in the ADRB2 gene had a larger waist circumference (P<0.05). Subjects of high SES with the ApoB 4145Lys allele had a larger mean waist circumference than those without this allele (P<0.05). Only in the presence of an adverse environment (low SES) did carriers of the NOS3 298Asp allele have a larger mean body mass index, waist circumference and sum of skinfolds (P<0.05).

Conclusion:

These results suggest that several polymorphisms are associated with the mean level of adiposity, with the effects depending on other factors such as race, sex and/or SES.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Figure 1
Figure 2

References

  1. Maes HH, Neale MC, Eaves LJ . Genetic and environmental factors in relative body weight and human adiposity. Behav Genet 1997; 27: 325–351.

    Article  CAS  Google Scholar 

  2. Loos RJ, Bouchard C . Obesity – is it a genetic disorder? J Intern Med 2003; 254: 401–425.

    Article  CAS  Google Scholar 

  3. Strauss RS, Pollack HA . Epidemic increase in childhood overweight, 1986–1998. JAMA 2001; 286: 2845–2848.

    Article  CAS  Google Scholar 

  4. Troiano RP, Flegal KM . Overweight children and adolescents: description, epidemiology, and demographics. Pediatrics 1998; 101: 497–504.

    CAS  PubMed  Google Scholar 

  5. Pastor P, Makuc DM, Reuben C, Xia H . Chartbook on trends in the health of Americans. Health, United States, 2002. National Center for Health Statistics: Hyattsville, Maryland, 2002.

    Google Scholar 

  6. Whitaker RC, Wright JA, Pepe MS, Seidel KD, Dietz WH . Predicting obesity in young adulthood from childhood and parental obesity. N Engl J Med 1997; 337: 869–873.

    Article  CAS  Google Scholar 

  7. Bao W, Srinivasan SR, Valdez R, Greenlund KJ, Wattigney WA, Berenson GS . Longitudinal changes in cardiovascular risk from childhood to young adulthood in offspring of parents with coronary artery disease: the Bogalusa Heart Study. JAMA 1997; 278: 1749–1754.

    Article  CAS  Google Scholar 

  8. Rankinen T, Zuberi A, Chagnon YC, Weisnagel SJ, Argyropoulos G, Walts B et al. The human obesity gene map: the 2005 update. Obesity (Silver Spring) 2006; 14: 529–644.

    Article  Google Scholar 

  9. Ellsworth DL, Coady SA, Chen W, Srinivasan SR, Elkasabany A, Gustat J et al. Influence of the beta2-adrenergic receptor Arg16Gly polymorphism on longitudinal changes in obesity from childhood through young adulthood in a biracial cohort: the Bogalusa Heart Study. Int J Obes Relat Metab Disord 2002; 26: 928–937.

    Article  CAS  Google Scholar 

  10. Dekkers JC, Podolsky RH, Treiber FA, Barbeau P, Gutin B, Snieder H . Development of general and central obesity from childhood into early adulthood in African American and European American males and females with a family history of cardiovascular disease. Am J Clin Nutr 2004; 79: 661–668.

    Article  CAS  Google Scholar 

  11. Dekkers JC, Snieder H, Van den Oord EJCG, Treiber FA . Moderators of blood pressure development from childhood to adulthood: a 10-year longitudinal study in African- and European American youth. J Pediatr 2002; 141: 770–779.

    Article  Google Scholar 

  12. Dekkers C, Treiber FA, Kapuku G, Van Den Oord EJ, Snieder H . Growth of left ventricular mass in African American and European American youth. Hypertension 2002; 39: 943–951.

    Article  CAS  Google Scholar 

  13. Elizalde M, Ryden M, van Harmelen V, Eneroth P, Gyllenhammar H, Holm C et al. Expression of nitric oxide synthases in subcutaneous adipose tissue of nonobese and obese humans. J Lipid Res 2000; 41: 1244–1251.

    CAS  PubMed  Google Scholar 

  14. Ryden M, Elizalde M, van Harmelen V, Ohlund A, Hoffstedt J, Bringman S et al. Increased expression of eNOS protein in omental versus subcutaneous adipose tissue in obese human subjects. Int J Obes Relat Metab Disord 2001; 25: 811–815.

    Article  CAS  Google Scholar 

  15. Treiber FA, Davis H, Musante L, Raunikar RA, Strong WB, McCaffrey F et al. Ethnicity, gender, family history of myocardial infarction, and hemodynamic responses to laboratory stressors in children. Health Psychol 1993; 12: 6–15.

    Article  CAS  Google Scholar 

  16. Dysart JM, Treiber FA, Pflieger K, Davis H, Strong WB . Ethnic differences in the myocardial and vascular reactivity to stress in normotensive girls. Am J Hypertens 1994; 7: 15–22.

    Article  CAS  Google Scholar 

  17. Dekkers JC, Treiber FA, Kapuku G, Snieder H . Differential influence of family history of hypertension and premature myocardial infarction on systolic blood pressure and left ventricular mass trajectories in youth. Pediatrics 2003; 111: 1387–1393.

    Article  Google Scholar 

  18. Treiber FA, Musante L, Kapuku G, Davis C, Litaker M, Davis H . Cardiovascular (CV) responsivity and recovery to acute stress and future CV functioning in youth with family histories of CV disease: a 4-year longitudinal study. Int J Psychophysiol 2001; 41: 65–74.

    Article  CAS  Google Scholar 

  19. Daniels SR, Khoury PR, Morrison JA . Utility of different measures of body fat distribution in children and adolescents. Am J Epidemiol 2000; 152: 1179–1184.

    Article  CAS  Google Scholar 

  20. Snieder H, Dong Y, Barbeau P, Harshfield GA, Dalageogou C, Zhu HD et al. beta2-adrenergic receptor gene and resting hemodynamics in European and African American youth. Am J Hypertens 2002; 15: 973–979.

    Article  CAS  Google Scholar 

  21. Widen E, Lehto M, Kanninen T, Walston J, Shuldiner AR, Groop LC . Association of a polymorphism in the beta 3-adrenergic-receptor gene with features of the insulin resistance syndrome in Finns. N Engl J Med 1995; 333: 348–351.

    Article  CAS  Google Scholar 

  22. Russ AP, Maerz W, Ruzicka V, Stein U, Gross W . Rapid detection of the hypertension-associated Met235--&gt;Thr allele of the human angiotensinogen gene. Hum Mol Genet 1993; 2: 609–610.

    Article  CAS  Google Scholar 

  23. Hansen PS, Gerdes LU, Klausen IC, Gregersen N, Faergeman O . Polymorphisms in the apolipoprotein B-100 gene contributes to normal variation in plasma lipids in 464 Danish men born in 1948. Hum Genet 1993; 91: 45–50.

    Article  CAS  Google Scholar 

  24. Jeerooburkhan N, Jones LC, Bujac S, Cooper JA, Miller GJ, Vallance P et al. Genetic and environmental determinants of plasma nitrogen oxides and risk of ischemic heart disease. Hypertension 2001; 38: 1054–1061.

    Article  CAS  Google Scholar 

  25. Wilson AG, di Giovine FS, Blakemore AI, Duff GW . Single base polymorphism in the human tumour necrosis factor alpha (TNF alpha) gene detectable by NcoI restriction of PCR product. Hum Mol Genet 1992; 1: 353.

    Article  CAS  Google Scholar 

  26. Dong Y, Zhu H, Sagnella GA, Carter ND, Cook DG, Cappuccio FP . Association between the C825T polymorphism of the G protein b3-subunit gene and hypertension in blacks. Hypertension 1999; 34: 1193–1196.

    Article  CAS  Google Scholar 

  27. Gotoda T, Manning BS, Goldstone AP, Imrie H, Evans AL, Strosberg AD et al. Leptin receptor gene variation and obesity: lack of association in a white British male population. Hum Mol Genet 1997; 6: 869–876.

    Article  CAS  Google Scholar 

  28. Zee RY, Schrader AP, Robinson BG, Griffiths LR, Morris BJ . Association of HincII RFLP of low density lipoprotein receptor gene with obesity in essential hypertensives. Clin Genet 1995; 47: 118–121.

    Article  CAS  Google Scholar 

  29. Deeb SS, Fajas L, Nemoto M, Pihlajamaki J, Mykkanen L, Kuusisto J et al. A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nat Genet 1998; 20: 284–287.

    Article  CAS  Google Scholar 

  30. Walder K, Norman RA, Hanson RL, Schrauwen P, Neverova M, Jenkinson CP et al. Association between uncoupling protein polymorphisms (UCP2-UCP3) and energy metabolism/obesity in Pima indians. Hum Mol Genet 1998; 7: 1431–1435.

    Article  CAS  Google Scholar 

  31. Goldstein H, Browne W, Rasbash J . Multilevel modelling of medical data. Stat Med 2002; 21: 3291–3315.

    Article  Google Scholar 

  32. Benjamini Y, Hochberg Y . Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Royal Stat Soc B 1995; 57: 289–300.

    Google Scholar 

  33. van Rossum CT, Hoebee B, Seidell JC, Bouchard C, van Baak MA, de Groot CPGM et al. Genetic factors as predictors of weight gain in young adult Dutch men and women. Int J Obes Relat Metab Disord 2002; 26: 517–528.

    Article  CAS  Google Scholar 

  34. van Rossum CT, Hoebee B, van Baak MA, Mars M, Saris WH, Seidell JC . Genetic variation in the leptin receptor gene, leptin, and weight gain in young Dutch adults. Obes Res 2003; 11: 377–386.

    Article  CAS  Google Scholar 

  35. Ellsworth DL, Coady SA, Chen W, Srinivasan SR, Boerwinkle E, Berenson GS . Interactive effects between polymorphisms in the beta-adrenergic receptors and longitudinal changes in obesity. Obes Res 2005; 13: 519–526.

    Article  CAS  Google Scholar 

  36. Masuo K, Katsuya T, Fu Y, Rakugi H, Ogihara T, Tuck ML . Beta2- and beta3-adrenergic receptor polymorphisms are related to the onset of weight gain and blood pressure elevation over 5 years. Circulation 2005; 111: 3429–3434.

    Article  CAS  Google Scholar 

  37. Wong MY, Day NE, Luan JA, Chan KP, Wareham NJ . The detection of gene–environment interaction for continuous traits: should we deal with measurement error by bigger studies or better measurement? Int J Epidemiol 2003; 32: 51–57.

    Article  CAS  Google Scholar 

  38. Phillips A . Commentary: balancing quantity and quality when designing epidemiological studies. Int J Epidemiol 2003; 32: 58–59.

    Article  Google Scholar 

  39. Herbert A, Gerry NP, McQueen MB, Heid IM, Pfeufer A, Illig T et al. A common genetic variant is associated with adult and childhood obesity. Science 2006; 312: 279–283.

    Article  CAS  Google Scholar 

  40. Lange C, van Steen K, Andrew T, Lyon H, DeMeo DL, Raby B et al. A family-based association test for repeatedly measured quantitative traits adjusting for unknown environmental and/or polygenic effects. Stat Appl Genet Mol Biol 2004; 3, Article17.

    Article  Google Scholar 

  41. Fabsitz RR, Carmelli D, Hewitt JK . Evidence for independent genetic influences on obesity in middle age. Int J Obes Relat Metab Disord 1992; 16: 657–666.

    CAS  PubMed  Google Scholar 

  42. Rice T, Perusse L, Bouchard C, Rao DC . Familial aggregation of body mass index and subcutaneous fat measures in the longitudinal Quebec family study. Genet Epidemiol 1999; 16: 316–334.

    Article  CAS  Google Scholar 

  43. Corbalán MS, Marti A, Forga L, Martinez-Gonzalez MA, Martinez JA . The risk of obesity and the Trp64Arg polymorphism of the beta(3)-adrenergic receptor: effect modification by age. Ann Nutr Metab 2002; 46: 152–158.

    Article  Google Scholar 

  44. Wang X, Thayer JF, Treiber F, Snieder H . Ethnic differences and heritability of heart rate variability in African- and European American youth. Am J Cardiol 2005; 96: 1166–1172.

    Article  Google Scholar 

  45. Meirhaeghe A, Helbecque N, Cottel D, Amouyel P . Beta2-adrenoceptor gene polymorphism, body weight, and physical activity. Lancet 1999; 353: 896.

    Article  CAS  Google Scholar 

  46. Martinez JA, Corbalan MS, Sanchez-Villegas A, Forga L, Marti A, Martinez-Gonzalez MA . Obesity risk is associated with carbohydrate intake in women carrying the Gln27Glu beta2-adrenoceptor polymorphism. J Nutr 2003; 133: 2549–2554.

    Article  CAS  Google Scholar 

  47. Marti A, Corbalan MS, Martinez-Gonzalez MA, Martinez JA . TRP64ARG polymorphism of the beta 3-adrenergic receptor gene and obesity risk: effect modification by a sedentary lifestyle. Diabetes Obes Metab 2002; 4: 428–430.

    Article  CAS  Google Scholar 

  48. Gutersohn A, Naber C, Muller N, Erbel R, Siffert W . G protein beta3 subunit 825 TT genotype and post-pregnancy weight retention. Lancet 2000; 355: 1240–1241.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study is supported in part by grant HL 69999 from the National Heart, Lung and Blood Institute and a State of Georgia Biomedical Initiative grant to the Georgia Center for the Prevention of Obesity and Related Disorders (GCORD).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to R H Podolsky or H Snieder.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Podolsky, R., Barbeau, P., Kang, HS. et al. Candidate genes and growth curves for adiposity in African- and European-American youth. Int J Obes 31, 1491–1499 (2007). https://doi.org/10.1038/sj.ijo.0803673

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijo.0803673

Keywords

This article is cited by

Search

Quick links