Abstract
AIMS: Multiple genes are likely to be involved in obesity and these genes may interact with environmental factors to influence obesity risk. Our aim was to explore the synergistic contribution of the two polymorphisms: Pro12Ala of the PPARγ2 gene and Trp64Arg of the ADRβ3 gene to obesity risk in a Spanish children and adolescent population.
METHODS: We designed a sex- and age-matched case–control study. Participants were 185 obese and 185 control children (aged 5–18 y) from the Navarra region, recruited through Departments of Pediatrics (Hospital Virgen del Camino, Navarra University Clinic and several Primary Health Centers). The obesity criterion (case definition) was BMI above the 97th percentile according to Spanish BMI reference data for age and gender. Anthropometric parameters were measured by standard protocols. The genotype was assessed by PCR-RFLP after digestion with BstUI for PPARγ2 mutation and BstNI for ADRβ3 variants. Face-to-face interviews were conducted to assess the physical activity. Using a validated physical activity questionnaire, we computed an activity metabolic equivalent index (METs h/week), which represents the physical exercise during the week for each participant. Statistical analysis was performed by conditional logistic regression, taking into account the matching between cases and controls.
RESULTS: Carriers of the polymorphism Pro12Ala of the PPARγ2 gene had a significantly higher obesity risk than noncarriers (odds ratio (OR)=2.18, 95% CI=1.09–4.36) when we adjusted for sex, age and physical activity. Moreover, the risk of obesity was higher (OR=2.59, 95% CI=1.17–5.34) when family history of obesity was also taken into account in the model. The OR for obesity linked to both polymorphisms (PPARγ2 and ADRβ3) was 5.30 (95% CI=1.08–25.97) when we adjusted for sex, age and physical activity. After adjustment for family history of obesity, the OR for carriers of both polymorphisms was 19.5 (95% CI=2.43–146.8).
CONCLUSIONS: A synergistic effect between polymorphism Pro12Ala of the PPARγ2 gene and Trp64Arg of the ADRβ3 gene for obesity risk was found in a case–control study including children and adolescents.
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References
Snyder EE, Walts B, Perusse L, Chagnon YC, Weisnagel SJ, Rankinen T, Bouchard C . The human obesity gene map: the 2003 update. Obes Res 2004; 12: 369–439.
Martinez JA . Obesity in young Europeans: genetic and environmental influences. Eur J Clin Nutr 2000; 54 (Suppl 1): S56–S60.
Buettner R, Schaffler A, Arndt H, Rogler G, Nusser J, Zietz B, Enger I, Hugl S, Cuk A, Scholmerich J, Palitzsch KD . The Trp64Arg polymorphism of the beta 3-adrenergic receptor gene is not associated with obesity or type 2 diabetes mellitus in a large population-based Caucasian cohort. J Clin Endocrinol Metab 1998; 83: 2892–2897.
Hamann A, Munzberg H, Buttron P, Busing B, Hinney A, Mayer H, Siegfried W, Hebebrand J, Greten H . Missense variants in the human peroxisome proliferator-activated receptor-gamma2 gene in lean and obese subjects. Eur J Endocrinol 1999; 141: 90–92.
Corella D, Guillen M, Portoles O, Sorli JV, Alonso V, Folch J, Saiz C . Gender specific associations of the Trp64Arg mutation in the beta3-adrenergic receptor gene with obesity-related phenotypes in a Mediterranean population: interaction with a common lipoprotein lipase gene variation. J Intern Med 2001; 250: 348–360.
Gonzalez Sanchez JL, Serrano Rios M, Fernandez Perez C, Laakso M, Martinez Larrad MT . Effect of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor gamma-2 gene on adiposity, insulin sensitivity and lipid profile in the Spanish population. Eur J Endocrinol 2002; 147: 495–501.
Marti A, Corbalan MS, Martinez-Gonzalez MA, Forga L, Martinez JA . CHO intake alters obesity risk associated with Pro12Ala polymorphism of PPARgamma gene. J Physiol Biochem 2002; 58: 219–220.
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.
Hinney A, Lentes KU, Rosenkranz K, Barth N, Roth H, Ziegler A, Hennighausen K, Coners H, Wurmser H, Jacob K, Romer G, Winnikes U, Mayer H, Herzog W, Lehmkuhl G, Poustka F, Schmidt MH, Blum WF, Pirke KM, Schafer H, Grzeschik KH, Remschmidt H, Hebebrand J . Beta 3-adrenergic-receptor allele distributions in children, adolescents and young adults with obesity, underweight or anorexia nervosa. Int J Obes Relat Metab Disord 1997; 21: 224–230.
Ochoa MC, Mdel C, Marti A, Martinez JA . Obesity studies in candidate genes. Med Clin (Barc) 2004; 122: 542–551.
Hsueh WC, Cole SA, Shuldiner AR, Beamer BA, Blangero J, Hixson JE, MacCluer JW, Mitchell BD . Interactions between variants in the beta3-adrenergic receptor and peroxisome proliferator-activated receptor-gamma2 genes and obesity. Diabetes Care 2001; 24: 672–677.
Corbalan 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.
Franks PW, Luan J, Browne PO, Harding AH, O'Rahilly S, Chatterjee VK, Wareham NJ . Does peroxisome proliferator-activated receptor gamma genotype (Pro12ala) modify the association of physical activity and dietary fat with fasting insulin level? Metabolism 2004; 53: 11–16.
Chasan-Taber S, Rimm EB, Stampfer MJ, Spiegelman D, Colditz GA, Giovannucci E, Ascherio A, Willett WC . Reproducibility and validity of a self-administered physical activity questionnaire for male health professionals. Epidemiology 1996; 7: 81–86.
Martinez-Gonzalez MA, Varo JJ, Santos JL, De Irala J, Gibney M, Kearney J, Martinez JA . Prevalence of physical activity during leisure time in the European Union. Med Sci Sports Exerc 2001; 33: 1142–1146.
Sivenius K, Valve R, Lindi V, Niskanen L, Laakso M, Uusitupa M . Synergistic effect of polymorphisms in uncoupling protein 1 and beta3-adrenergic receptor genes on long-term body weight change in Finnish type 2 diabetic and non-diabetic control subjects. Int J Obes Relat Metab Disord 2000; 24: 514–519.
Proenza AM, Poissonnet CM, Ozata M, Ozen S, Guran S, Palou A, Strosberg AD . Association of sets of alleles of genes encoding beta3-adrenoreceptor, uncoupling protein 1 and lipoprotein lipase with increased risk of metabolic complications in obesity. Int J Obes Relat Metab Disord 2000; 24: 93–100.
Fogelholm M, Valve R, Kukkonen-Harjula K, Nenonen A, Hakkarainen V, Laakso M, Uusitupa M . Additive effects of the mutations in the beta3-adrenergic receptor and uncoupling protein-1 genes on weight loss and weight maintenance in Finnish women. J Clin Endocrinol Metab 1998; 83: 4246–4250.
Masud S, Ye S . Effect of the peroxisome proliferator activated receptor-gamma gene Pro12Ala variant on body mass index: a meta-analysis. J Med Genet 2003; 40: 773–780.
Neutzling MB, Taddei JA, Gigante DP . Risk factors of obesity among Brazilian adolescents: a case–control study. Public Health Nutr 2003; 6: 743–749.
Oliveira SA, Mansur AP, Ribeiro CC, Ramires JA, Annichino-Bizzacchi JM . PON1 M/L55 mutation protects high-risk patients against coronary artery disease. Int J Cardiol 2004; 94: 73–77.
Maffeis C, Talamini G, Tato L . Influence of diet, physical activity and parents' obesity on children's adiposity: a four-year longitudinal study. Int J Obes Relat Metab Disord 1998; 22: 758–764.
Umekawa T, Yoshida T, Sakane N, Kogure A, Kondo M, Honjyo H . Trp64Arg mutation of beta3-adrenoceptor gene deteriorates lipolysis induced by beta3-adrenoceptor agonist in human omental adipocytes. Diabetes 1999; 48: 117–120.
Acknowledgements
We are grateful for the participation of subjects and their families and the collaboration of the medical teams from hospitals and health centers involved in the study. This work was supported by grants from the Navarra Government (Departamento de Salud) and Linea Especial—Nutrición y Obesidad (University of Navarra). We are grateful for the technical assistance of Ana Lorente.
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Ochoa, M., Marti, A., Azcona, C. et al. Gene–gene interaction between PPARγ2 and ADRβ3 increases obesity risk in children and adolescents. Int J Obes 28 (Suppl 3), S37–S41 (2004). https://doi.org/10.1038/sj.ijo.0802803
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DOI: https://doi.org/10.1038/sj.ijo.0802803
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