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Genetic factors as predictors of weight gain in young adult Dutch men and women

International Journal of Obesity volume 26, pages 517–528 (2002)Cite this article

Abstract

OBJECTIVE: To investigate the association between DNA polymorphisms in several candidate genes for obesity and weight gain. Polymorphisms in these genes may contribute to weight gain through effects on energy intake, energy expenditure or adipogenesis.

DESIGN AND METHODS: From two large cohorts in the Netherlands (total 17 500 adult men and women), we compared 286 subjects aged 20–40 y who gained an average of 12.8 kg (range 5.5–47 kg) during a mean follow-up of 6.8 y with 296 subjects who remained relatively constant over the same period with respect to occurrence of several polymorphisms in candidate genes of obesity and some lifestyle factors. Subjects who were dieting, were high alcohol consumers, were pregnant, changed their smoking status recently, or those who suffered from serious illnesses were excluded. Polymorphisms were determined in the LEPR-gene (LEPR Lys109Arg, LEPR Gln223Arg, LEPR Lys656Asn), in the UCP1 gene (A–G mutation at position-3826 5′region), in the UCP2 gene (Ala55Val, 45 bp Ins/Del), in the PPARG2 gene (Prol2Ala) and in the ADRB2 gene (Gly16Arg and Gln27Glu).

RESULTS: With the exception of the Gly16Arg polymorphism in the ADRB2 gene in men (P=0.04) and women (P=0.05), and the Lys109Arg polymorphism in the LEPR gene in women, no statistically significant differences in the genotype and allele frequencies were observed between weight gainers and non-weight gainers. Weight gainers differed in some aspects of dietary habits and physical activity patterns: weight gainers consumed relatively more savory snacks and were less active during leisure time compared with non-weight gainers.

CONCLUSION: Only variations in the ADRB2 gene and LEPR gene, may contribute to susceptibility to weight gain. None of the other studied genetic markers were clearly associated with weight gain. Further research is necessary to establish the role of lifestyle factors, or interactions between genes or between genes and lifestyle factors on weight gain with age.

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References

  1. WHO . Obesity: preventing and managing the global epidemic WHO: Geneva 1997.

    Google Scholar 

  2. Hill JO, Peters JC . Environmental contributions to the obesity epidemic Science 1998 280: 1371–1374.

    Article  CAS  PubMed  Google Scholar 

  3. Lindroos AK, Lissner L, Carlsson B, Carlsson LM, Torgerson J, Karlsson C, Stenlöf K, Sjöström L . Familial predisposition for obesity may modify the predictive value of serum leptin concentrations for long-term weight change in obese women Am J Clin Nutr 1998 67: 1119–1123.

    Article  CAS  PubMed  Google Scholar 

  4. Stunkard AJ, Harris JR, Pedersen NL, McClearn GE . The body-mass index of twins who have been reared apart New Engl J Med 1990 322: 1483–1487.

    Article  CAS  PubMed  Google Scholar 

  5. Bouchard C, Tremblay A, Després J-P, Nadeau A, Lupien PJ, Thériault G, Dussault J, Moorjani S, Pinault S, Fournier G . The response to long-term overfeeding in identical twins New Engl J Med 1990 322: 1477–1482.

    Article  CAS  PubMed  Google Scholar 

  6. Comuzzie AG, Allison DB . The search for human obesity genes Science 1998 280: 1374–1377.

    Article  CAS  PubMed  Google Scholar 

  7. Barsh GS, Farooqi IS, O'Rahilly S . Genetics of body-weight regulation Nature 2000 404: 644–651.

    Article  CAS  PubMed  Google Scholar 

  8. Chagnon YC, Pérusse L, Weisnagel SJ, Rankinen T, Bouchard C . The human obesity gene map: the 1999 update Obes Res 2000 8: 89–117.

    Article  CAS  PubMed  Google Scholar 

  9. Schrauwen P, Walden K, Ravussin E . Human uncoupling proteins and obesity Obes Res 1999 7: 97–105.

    Article  CAS  PubMed  Google Scholar 

  10. Frühbeck G, Salvador J . Relation between leptin and the regulation of glucose metabolism Diabetologia 2000 43: 1.

    Article  Google Scholar 

  11. Lönnqvist F, Nordfors L, Schalling M . Leptin and its potential role in human obesity J Intern Med 1999 245: 643–652.

    Article  PubMed  Google Scholar 

  12. Auwerx J . PPARgamma, the ultimate thrifty gene Diabetologia 1999 42: 1033–1049.

    Article  CAS  PubMed  Google Scholar 

  13. Arner P, Hoffstedt J . Adrenoceptor genes in human obesity J Intern Med 1999 245: 667–672.

    Article  CAS  PubMed  Google Scholar 

  14. Verschuren WMM, van Leer EM, Blokstra A, Seidell JC, Smit HA, Bueno de Mesquita HB, Obermann-de Boer GL, Kromhout D . Cardiovascular disease risk factors in The Netherlands Neth J Cardiol 1993 6: 205–210.

    Google Scholar 

  15. Korkeila M, Kaprio J, Rissanen A, Koskenvuo M . Consistency and change of body mass index and weight. A study on 5967 adult Finnish twin pairs Int J Obes Relat Metab Disord 1995 19: 310–317.

    CAS  PubMed  Google Scholar 

  16. Bloemberg BPM . On the effect of measurement error in nutritional epidemiology using dietary history and food frequency methodology Leiden: Rijksuniversiteit Leiden 1993.

  17. Walder K, Norman RA, Hanson RL, Schrauwen P, Neverova M, Jenkinson CP, Easlick J, Warden CH, Pecqueur C, Raimbault S, Ricquier D, Silver MHK, Shuldiner AR, Solanes G, Lowell BB, Chung WK, Leibel RL, Pratley R, Ravussin E . Association between uncoupling protein polymorphisms (UCP2-UCP3) and energy metabolism/obesity in Pima Indians Hum Mol Genet 1998 7: 1431–1435.

    Article  CAS  PubMed  Google Scholar 

  18. Cassard-Doulcier AM, Bouillaud F, Chagnon M, Gelly C, Dionne FT, Oppert JM, Bouchard C, Chagnon Y, Ricquier D . The Bcl I polymorphism of the human uncoupling protein (ucp) gene is due to a point mutation in the 5′-flanking region Int J Obes Relat Metab Disord 1996 20: 278–279.

    CAS  PubMed  Google Scholar 

  19. Yen C-J, Beamer BA, Negri C, Silver K, Brown KA, Yarnall DP, Burns DK, Roth J, Shuldiner AR . Molecular scanning of the human peroxisome proliferator activated receptor gamma (hPPARgamma) gene in diabetic Caucasians: identification of a Pro12Ala PPAR gamma 2 missense mutation Biochem Biophys Res Commun 1997 241: 270–274.

    Article  CAS  PubMed  Google Scholar 

  20. Chung WK, Kehoe LP, Chua M, Chu F, Aronne L, Huma Z, Sothern M, Udall JN, Kahle B, Leibel RL . Exonic and intronic sequence variation in the human leptin receptor gene (LEPR) Diabetes 1997 46: 1509–1511.

    Article  CAS  PubMed  Google Scholar 

  21. Large V, Hellström L, Reynisdottir S, Lönnqvist F, Eriksson P, Lannfelt L, Arner P . Human beta-2 adrenoceptor gene polymorphisms are highly frequent in obesity and associate with altered adipocyte beta-2 adrenoceptor function J Clin Invest 1997 100: 3005–3013.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Echwald SM, Sørensen TD, Sørensen TIA, Hansen AT-H, Andersen T, Chung WK, Leibel RL, Pedersen O . Amino acid variants in the human leptin receptor: lack of association to juvenile onset obesity Biochem Biophys Res Commun 1997 233: 248–252.

    Article  CAS  PubMed  Google Scholar 

  23. Schaid DJ, Jacobsen SJ . Baised tests of association: comparisons of allele frequencies when departing from Hardy-Weinberg proportions Am J Epidemiol 1999 149: 706–711.

    Article  CAS  PubMed  Google Scholar 

  24. Ravussin E, Gautier J-F . Metabolic predictors of weight gain Int J Obes Relat Metab Disord 1999 23(Suppl 1): 37–41.

    Article  PubMed  Google Scholar 

  25. Rowland ML . Self-reported weight and height Am J Clin Nutr 1990 52: 1125–1133.

    Article  CAS  PubMed  Google Scholar 

  26. Meirhaeghe A, Helbecque N, Cottel D, Amouyel P . Impact of polymorphisms of the human beta2-adrenoceptor gene on obesity in a French population Int J Obes Relat Metab Disord 2000 24: 382–387.

    Article  CAS  PubMed  Google Scholar 

  27. Ishiyama-Shigemoto S, Yamada X, Ichikawa K, Nonaka K . Association of polymorphism in the beta2-arenergic receptor gene with obesity, hypertriglyceridaemia, and diabetes mellitus Diabetologia 1999 42: 98–101.

    Article  CAS  PubMed  Google Scholar 

  28. Hellström L, Large V, Reynisdottir S, Wahrenberg H, Arner P . The different effects of a Gln27Glu beta(2)-adrenoceptor gene polymorphism on obesity in males and in females J Intern Med 1999 245: 253–259.

    Article  PubMed  Google Scholar 

  29. Mori Y, Kim-Motoyama H, Ito Y, Katakura T, Yasuda K, Ishiyama-Shigemoto S, Yamada K, Akanuma Y, Ohashi Y, Kimura S, Yazaki Y, Kadowaki T . The Gln27Glu beta2-adrenergic receptor variant is associated with obesity due to subcutaneous fat accumulation in Japanese men Biochem Biophys Res Commun 1999 258: 138–140.

    Article  CAS  PubMed  Google Scholar 

  30. Cassell PG, Neverova M, Janmohamed S, Uwakwe N, Qureshi A, McCarthy MI, Saker PJ, Albon L, Kopelman P, Noonan K, Easlick J, Ramachandran A, Snehalatha C, Pecqueur C, Ricquier D, Warden C, Hitman GA . An uncoupling protein 2 gene variant is associated with a raised body mass index but not type II diabetes Diabetologia 1999 42: 688–692.

    Article  CAS  PubMed  Google Scholar 

  31. Astrup A, Toubro S, Dalgaard LT, Urhammer SA, Sørensen TIA, Pederson O . Impact of the v/v 55 polymorphism of the uncoupling protein 2 gene on 24-h energy expenditure and substrate oxidation Int J Obes Relat Metab Disord 1999 23: 1030–1034.

    Article  CAS  PubMed  Google Scholar 

  32. Clément K, Ruiz J, Cassard-Doulcier AM, Bouillaud F, Ricquier D, Basdevant A, Guy-Grand B, Froguel P . Additive effect of A→G (−3826) variant of the uncoupling protein gene and the Trp64Arg mutation of the beta 3-adrenergic receptor gene on weight gain in morbid obesity Int J Obes Relat Metab Disord 1996 20: 1062–1066.

    PubMed  Google Scholar 

  33. Fumeron F, Durack-Bown I, Betoulle D, Cassard-Doulcier AM, Tuzet S, Bouillaud F, Melchior JC, Ricquier D, Apfelbaum M . Polymorphisms of uncoupling protein (UCP) and beta 3 adrenoreceptor genes in obese people submitted to a low calorie diet Int J Obes Relat Metab Disord 1996 20: 1051–1054.

    CAS  PubMed  Google Scholar 

  34. Oppert J-M, Vohl MC, Chagnon M, Dionne FT, Cassard-Doulcier AM, Ricquier D, Pérusse L, Bouchard C . DNA polymorphism in the uncoupling protein (UCP) gene and human body fat Int J Obes Relat Metab Disord 1994 18: 526–531.

    CAS  PubMed  Google Scholar 

  35. Thompson DB, Ravussin E, Bennett PH, Bogardus C . Structure and sequence variation at the human leptin receptor gene in lean and obese Pima Indians Hum Mol Genet 1997 6: 675–679.

    Article  CAS  PubMed  Google Scholar 

  36. Rosmond R, Chagnon YC, Holm G, Chagnon M, Perusse L, Lindell K, Carlsson B, Bouchard C, Bjorntorp P . Hypertension in obesity and the leptin receptor gene locus J Clin Endocrinol Metab 2000 85: 3126–3131.

    CAS  PubMed  Google Scholar 

  37. Gotoda T, Manning BS, Goldstone AP, Imrie H, Evans AL, Strosberg AD, McKeigue PM, Scott J, Aitman TJ . Leptin receptor gene variation and obesity: lack of association in a white British male population Hum Mol Genet 1997 6: 869–876.

    Article  CAS  PubMed  Google Scholar 

  38. Deeb SS, Fajas L, Nemoto M, Pihlajamaki J, Mykkänen L, Kuusisto J, Laakso M, Fujimoto W, Auwerx J . A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity Nature Genet 1998 20: 284–287.

    Article  CAS  PubMed  Google Scholar 

  39. Beamer BA, Yen C-J, Andersen RE, Muller D, Elahi D, Cheskin LJ, Andres R, Roth J, Shuldiner AR . Association of the Pro12Ala variant in the peroxisome proliferator-activated receptor gamma 2 gene with obesity in two Caucasian populations Diabetes 1998 47: 1806–1808.

    Article  CAS  PubMed  Google Scholar 

  40. Ek J, Urhammer SA, Sørensen TIA, Andersen T, Auwerx J, Pedersen O . Homozygosity of the Pro12Ala variant of the peroxisome proliferation-activated receptor-gamma2 (PPAR-gamma2): divergent modulating effects on body mass index in obese and lean Caucasian men Diabetologia 1999 42: 892–895.

    Article  CAS  PubMed  Google Scholar 

  41. Cole SA, Mitchell BD, Hsueh W-C, Pineda P, Beamer BA, Shuldiner AR, Comuzzie AG, Blangero J, Hixson JE . The Pro12Ala variant of peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2) is associated with measures of obesity in Mexican Americans Int J Obes Relat Metab Disord 2000 24: 522–524.

    Article  CAS  PubMed  Google Scholar 

  42. Meirhaeghe A, Fajas L, Helbecque N, Cottel D, Lebel P, Dallongeville J, Deeb S, Auwerx J, Amouyel P . A genetic polymorphism of the peroxisome proliferator-activated receptor gamma gene influences plasma leptin levels in obese humans Hum Mol Genet 1998 7: 435–440.

    Article  CAS  PubMed  Google Scholar 

  43. Oberkofler H, Esterbauer H, Hell E, Krempler F, Patsch W . The Gln27Glu polymorphism in the beta2-adrenergic receptor gene is not associated with morbid obesity in Austrian women Int J Obes Relat Metab Disord 2000 24: 388–390.

    Article  CAS  PubMed  Google Scholar 

  44. Kortner B, Wolf A, Wendt D, Beisiegel U, Evans D . Lack of association between a human beta-2 adrenoceptor gene polymorphism (gln27glu) and morbid obesity Int J Obes Relat Metab Disord 1999 23: 1099–1100.

    Article  CAS  PubMed  Google Scholar 

  45. Urhammer SA, Dalgaard LT, Sørensen TIA, Moller AM, Andersen T, Hansen AT-H, Hansen T, Clausen JO, Vestergaard H, Pedersen O . Mutational analysis of the coding region of the uncoupling protein 2 gene in obese NIDDM patients: impact of a common amino acid polymorphism on juvenile and maturity onset forms of obesity and insulin resistance Diabetologia 1997 40: 1227–1230.

    Article  CAS  PubMed  Google Scholar 

  46. Kubota T, Mori H, Tamori Y, Okazawa H, Fukuda T, Miki M, Ito C, Fleury C, Bouillaud F, Kasuga M . Molecular screening of uncoupling protein 2 gene in patients with noninsulin-dependent diabetes mellitus or obesity J Clin Endocrinol Metab 1998 83: 2800–2804.

    CAS  PubMed  Google Scholar 

  47. Dalgaard LT, Sørensen TIA, Andersen T, Hansen T, Pedersen O . An untranslated insertion variant in the uncoupling protein 2 gene is not related to body mass index and changes in body weight during a 26-year follow-up in Danish Caucasian men Diabetologia 1999 42: 1413–1416.

    Article  CAS  PubMed  Google Scholar 

  48. Urhammer SA, Fridberg M, Sørensen TIA, Echwald SM, Andersen T, Tybjaerg-Hansen A, Clausen JO, Pedersen O . Studies of genetic variability of the uncoupling protein 1 gene in Caucasian subjects with juvenile-onset obesity J Clin Endocrinol Metab 1997 82: 4069–4074.

    CAS  PubMed  Google Scholar 

  49. Gagnon J, Lago F, Chagnon YC, Pérusse L, Näslund I, Lissner L, Sjöström L, Bouchard C . DNA polymorphism in the uncoupling protein 1 (UCP1) gene has no effect on obesity related phenotypes in the Swedish Obese Subjects cohorts Int J Obes Relat Metab Disord 1998 22: 500–505.

    Article  CAS  PubMed  Google Scholar 

  50. Matsuoka N, Ogawa Y, Hosoda K, Matsuda J, Masuzaki H, Miyawaki T, Azuma N, Natsui K, Nishimura H, Yoshimasa Y, Nishi S, Thompson DB, Nakao K . Human leptin receptor gene in obese Japanese subjects: evidence against either obesity-causing mutations or association of sequence variants with obesity Diabetologia 1997 40: 1204–1210.

    Article  CAS  PubMed  Google Scholar 

  51. de Silva A, Walder K, Aitman T, Gotoda T, Goldstone A, Hodge A, de Courten M, Zimmet P, Collier G . Combination of polymorphisms in OB-R and the OB gene associated with insulin resistance in Nauruan males Int J Obes Relat Metab Disord 1999 23: 816–822.

    Article  Google Scholar 

  52. Clement K, Hercberg S, Passinge B, Galan P, Varroud-Vial M, Shuldiner AR, Beamer BA, Charpentier G, Guy-Grand B, Froguel P, Vaisse C . The Pro115Gln and Pro12Ala PPAR gamma gene mutations in obesity and type 2 diabetes Int J Obes Relat Metab Disord 2000 24: 391–393.

    Article  CAS  PubMed  Google Scholar 

  53. Valve R, Sivenius K, Miettinen R, Pihlajamäki J, Rissanen A, Deeb SS, Auwerx J, Uusitupa M, Laakso M . Two polymorphisms in the peroxisome proliferator-activated receptor-gamma gene are associated with severe overweight among obese women J Clin Endocrinol Metab 1999 84: 3708–3712.

    CAS  PubMed  Google Scholar 

  54. Green SA, Turki J, Hall IP, Liggett SB . Implications of genetic variability of human beta 2-adrenergic receptor structure Pulm Pharmac 1995 8: 1–10.

    Article  CAS  Google Scholar 

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Acknowledgements

The Cardiovascular Disease Risk Factor Monitoring Study (PEILSTATION) and the Monitoring Project on Risk Factors for Chronic Diseases (MORGEN-project) was financially supported by the Ministry of Health, Welfare and Sport of The Netherlands and the National Institute of Public Health and the Environment. The authors would like to thank the epidemiologists and field-workers of the Municipal Health Services in Doetinchem and Maastricht for their important contribution to the data collection for this study. The authors wish to thank GL Obermann-de Boer for coordinating the PEILSTATION-project. The project steering committee of MORGEN project consisted of Dr HB Bueno de Mesquita, Dr HA Smit, Dr WMM Verschuren and Dr JC Seidell (project leader). Project leader of the follow-up measurements in Maastricht was Dr AJ Schuit. Logistic management was provided by A Jansen and J Steenbrink and data management by A Blokstra, P Steinberger and A van Kessel. Furthermore, we gratefully acknowledge K Wichers and H Hodemaekers, who did a part of the PCR analyses. CTM van Rossum is supported by the Dutch Scientific Organization (NWO). C Bouchard is supported in part by the George A Bray Chair in Nutrition.

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Authors and Affiliations

  1. Department of Chronic Diseases Epidemiology, National Institute of Public Health and the Environment, Bilthoven, The Netherlands

    CTM van Rossum & JC Seidell

  2. Laboratory of Health Effects Research, National Institute of Public Health and the Environment, Bilthoven, The Netherlands

    B Hoebee

  3. Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana, USA

    C Bouchard & M Chagnon

  4. Department of Human Biology, Maastricht University, Maastricht, The Netherlands

    MA van Baak & WHM Saris

  5. Department of Human Nutrition and Epidemiology, Wageningen University, Wageningen, The Netherlands

    CPGM de Groot & C de Graaf

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  1. CTM van Rossum
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van Rossum, C., Hoebee, B., Seidell, J. et al. Genetic factors as predictors of weight gain in young adult Dutch men and women. Int J Obes 26, 517–528 (2002). https://doi.org/10.1038/sj.ijo.0801964

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