Breast-feeding Modulates the Influence of the Peroxisome Proliferator-activated Receptor-gamma (PPARG2) Pro12Ala Polymorphism on Adiposity in Adolescents: The Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) Cross-sectional Study

Overview

Journal Diabetes Care

Specialty Endocrinology

Date 2009 Oct 23

PMID 19846795

Citations 12

Authors

Caroline Verier

Aline Meirhaeghe

Szilvia Bokor

Christina Breidenassel

Yannis Manios

Denes Molnar

Enrique G Artero

Esther Nova

Stefaan de Henauw

Luis A Moreno

Philippe Amouyel

Idoia Labayen

Noemi Bevilacqua

Dominique Turck

Laurent Beghin

Jean Dallongeville

Frederic Gottrand

Affiliations

Soon will be listed here.

Abstract

Objective: The peroxisome proliferator-activated receptor-gamma2 (PPARG2) Pro12Ala polymorphism has been associated with a higher BMI and a lower risk of type 2 diabetes in adulthood. The association between adiposity and PPARG variants can be influenced by environmental factors such as early growth, dietary fat, and (as recently shown) breast-feeding. The objectives of this study were to assess 1) the influence of the PPARG2 Pro12Ala polymorphism on adiposity markers in adolescents and 2) a possible modulating effect of breast-feeding on these associations.

Research Design And Methods: Data on breast-feeding duration, BMI, and genotypes for the Pro12Ala polymorphism were available for 945 adolescents (mean age 14.7 years). The breast-feeding duration was obtained from parental records. We measured weight, height, waist circumference, and six skinfold thicknesses.

Results: No significant associations between the Pro12Ala polymorphism and any of the above-mentioned anthropometric parameters were found. There were significant interactions between the PPARG2 Pro12Ala polymorphism and breast-feeding with regard to adiposity measurements (all adjusted P < 0.05). Indeed, in children who had not been breast-fed, Ala12 allele carriers had higher adiposity parameters (e.g., Delta BMI +1.88 kg/m(2), adjusted for age, sex, and center, P = 0.007) than Pro12Pro adolescents. In contrast, in breast-fed subjects, there was no significant difference between Ala12 allele carriers and Pro12Pro children in terms of adiposity measurements, whatever the duration of breast-feeding.

Conclusions: Breast-feeding appears to counter the deleterious effect of the PPARG2 Pro12Ala polymorphism on anthropometric parameters in adolescents.

Citing Articles

From Pregnancy to Breastfeeding: The Role of Maternal Exercise in Preventing Childhood Obesity.

Calcaterra V, Cena H, Pirazzi A, Sottotetti F, Cordaro E, Cavallo C Nutrients. 2025; 17(4).

PMID: 40004988 PMC: 11858060. DOI: 10.3390/nu17040660.

Interaction between breastfeeding duration and an obesity genetic risk score to predict body fat composition in European adolescents: The HELENA study.

Baxevanis G, Iglesia I, Seral-Cortes M, Sabroso-Lasa S, Flores-Barrantes P, Gottrand F Pediatr Obes. 2025; 20(3):e13205.

PMID: 39835382 PMC: 11803183. DOI: 10.1111/ijpo.13205.

The interaction of breastfeeding and genetic factors on childhood obesity.

Danaie M, Yeganegi M, Dastgheib S, Bahrami R, Jayervand F, Rahmani A Eur J Obstet Gynecol Reprod Biol X. 2024; 23:100334.

PMID: 39224127 PMC: 11367475. DOI: 10.1016/j.eurox.2024.100334.

Cardiometabolic effects of breastfeeding on infants of diabetic mothers.

Elbeltagi R, Al-Beltagi M, Saeed N, Bediwy A World J Diabetes. 2023; 14(5):617-631.

PMID: 37273257 PMC: 10236993. DOI: 10.4239/wjd.v14.i5.617.

Personalized Nutrition Approach in Pregnancy and Early Life to Tackle Childhood and Adult Non-Communicable Diseases.

Alabduljabbar S, Al Zaidan S, Lakshmanan A, Terranegra A Life (Basel). 2021; 11(6).

PMID: 34073649 PMC: 8224671. DOI: 10.3390/life11060467.

References

Luan J, Browne P, Harding A, Halsall D, ORahilly S, Chatterjee V . Evidence for gene-nutrient interaction at the PPARgamma locus. Diabetes. 2001; 50(3):686-9. DOI: 10.2337/diabetes.50.3.686. View

Mook-Kanamori D, Steegers E, Uitterlinden A, Moll H, Van Duijn C, Hofman A . Breast-feeding modifies the association of PPARgamma2 polymorphism Pro12Ala with growth in early life: the Generation R Study. Diabetes. 2009; 58(4):992-8. PMC: 2661583. DOI: 10.2337/db08-1311. View

Hollenberg A, Susulic V, Madura J, Zhang B, Moller D, Tontonoz P . Functional antagonism between CCAAT/Enhancer binding protein-alpha and peroxisome proliferator-activated receptor-gamma on the leptin promoter. J Biol Chem. 1997; 272(8):5283-90. DOI: 10.1074/jbc.272.8.5283. View

Labayen I, Moreno L, Marti A, Gonzalez-Lamuno D, Warnberg J, Ortega F . Effect of the Ala12 allele in the PPARgamma-2 gene on the relationship between birth weight and body composition in adolescents: the AVENA study. Pediatr Res. 2007; 62(5):615-9. DOI: 10.1203/PDR.0b013e318156887a. View

Bennett A, Sovio U, Ruokonen A, Martikainen H, Pouta A, Hartikainen A . No evidence that established type 2 diabetes susceptibility variants in the PPARG and KCNJ11 genes have pleiotropic effects on early growth. Diabetologia. 2007; 51(1):82-5. DOI: 10.1007/s00125-007-0863-1. View

Tonjes A, Scholz M, Loeffler M, Stumvoll M . Association of Pro12Ala polymorphism in peroxisome proliferator-activated receptor gamma with Pre-diabetic phenotypes: meta-analysis of 57 studies on nondiabetic individuals. Diabetes Care. 2006; 29(11):2489-97. DOI: 10.2337/dc06-0513. View

Willer C, Speliotes E, Loos R, Li S, Lindgren C, Heid I . Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat Genet. 2008; 41(1):25-34. PMC: 2695662. DOI: 10.1038/ng.287. View

Harder T, Bergmann R, Kallischnigg G, Plagemann A . Duration of breastfeeding and risk of overweight: a meta-analysis. Am J Epidemiol. 2005; 162(5):397-403. DOI: 10.1093/aje/kwi222. View

Beamer B, Yen C, Andersen R, Muller D, Elahi D, Cheskin L . Association of the Pro12Ala variant in the peroxisome proliferator-activated receptor-gamma2 gene with obesity in two Caucasian populations. Diabetes. 1998; 47(11):1806-8. DOI: 10.2337/diabetes.47.11.1806. View

10.

Laitinen K, Hoppu U, Hamalainen M, Linderborg K, Moilanen E, Isolauri E . Breast milk fatty acids may link innate and adaptive immune regulation: analysis of soluble CD14, prostaglandin E2, and fatty acids. Pediatr Res. 2006; 59(5):723-7. DOI: 10.1203/01.pdr.0000203158.31452.9e. View

11.

Meirhaeghe A, Fajas L, Helbecque N, Cottel D, Auwerx J, Deeb S . Impact of the Peroxisome Proliferator Activated Receptor gamma2 Pro12Ala polymorphism on adiposity, lipids and non-insulin-dependent diabetes mellitus. Int J Obes Relat Metab Disord. 2000; 24(2):195-9. DOI: 10.1038/sj.ijo.0801112. View

12.

Lagou V, Scott R, Manios Y, Chen T, Wang G, Grammatikaki E . Impact of peroxisome proliferator-activated receptors gamma and delta on adiposity in toddlers and preschoolers in the GENESIS Study. Obesity (Silver Spring). 2008; 16(4):913-8. DOI: 10.1038/oby.2008.1. View

13.

Barker D . Intrauterine programming of adult disease. Mol Med Today. 1995; 1(9):418-23. DOI: 10.1016/s1357-4310(95)90793-9. View

14.

Cole S, Mitchell B, Hsueh W, Pineda P, Beamer B, Shuldiner A . 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(4):522-4. DOI: 10.1038/sj.ijo.0801210. View

15.

Zeggini E, Scott L, Saxena R, Voight B, Marchini J, Hu T . Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nat Genet. 2008; 40(5):638-45. PMC: 2672416. DOI: 10.1038/ng.120. View

16.

Memisoglu A, Hu F, Hankinson S, Manson J, De Vivo I, Willett W . Interaction between a peroxisome proliferator-activated receptor gamma gene polymorphism and dietary fat intake in relation to body mass. Hum Mol Genet. 2003; 12(22):2923-9. DOI: 10.1093/hmg/ddg318. View

17.

Meirhaeghe A, Boreham C, Murray L, Richard F, Davey Smith G, Young I . A possible role for the PPARG Pro12Ala polymorphism in preterm birth. Diabetes. 2007; 56(2):494-8. DOI: 10.2337/db06-0915. View

18.

Pihlajamaki J, Vanhala M, Vanhala P, Laakso M . The Pro12Ala polymorphism of the PPAR gamma 2 gene regulates weight from birth to adulthood. Obes Res. 2004; 12(2):187-90. DOI: 10.1038/oby.2004.25. View

19.

Eriksson J . The role of genes in growth and later health. Nestle Nutr Workshop Ser Pediatr Program. 2008; 61:69-77. DOI: 10.1159/000113171. View

20.

Deeb S, Fajas L, Nemoto M, Pihlajamaki J, Mykkanen L, Kuusisto J . A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nat Genet. 1998; 20(3):284-7. DOI: 10.1038/3099. View