(03-05-12) Analyses of single nucleotide polymorphisms in selected nutrient-sensitive genes in weight-regain prevention: the DIOGENES

study1,2,3,4
1. Lesli H Larsen,
2. Lars ?ngquist,
3. Karani S Vimaleswaran,
4. J?rg Hager,
5. Nathalie Viguerie,
6. Ruth JF Loos,
7. Teodora Handjieva-Darlenska,
8. Susan A Jebb,
9. Marie Kune?ova,
10. Thomas M Larsen,
11. J Alfredo Martinez,
12. Angeliki Papadaki,
13. Andreas FH Pfeiffer,
14. Marleen A van Baak,
15. Thorkild IA S?rensen,
16. Claus Holst,
17. Dominique Langin,
18. Arne Astrup, and
19. Wim HM Saris
+ Author Affiliations
1. 1From the Department of Human Nutrition, LIFE, University of Copenhagen, Copenhagen, Denmark (LHL, TML, and AA); Institute of Preventive Medicine, Copenhagen University Hospitals, Copenhagen, Denmark (L?, TIAS, and CH); MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, United Kingdom (KSV and RJFL); CEA Genomics Institute?Centre National de G?notypage, Evry, France (JH); Inserm U1048, Obesity Research Laboratory, Metabolic and Cardiovascular Medicine Institute, University of Toulouse, Toulouse, France (NV and DL); National Transport Hospital, Department of Nutrition, Dietetics and Metabolic Diseases, Sofia, Bulgaria (TH-D); MRC Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, United Kingdom (SAJ); The Obesity Management Center, Institute of Endocrinology, Prague, Czech Republic (MK); University of Navarra, Department of Physiology and Nutrition, Pamplona, Spain (JAM); the University of Crete, Department of Social Medicine, Rethymnon, Crete, Greece (AP); the German Institute of Human Nutrition, Department of Clinical Nutrition, Germany and Charit? Medical University, Department of Endocrinology, Diabetes & Nutrition, Berlin, Germany (AFHP); and the Department of Human Biology, NUTRIM School for Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre+, Maastricht, Netherlands (MAvB and WHMS).
+ Author Notes
↵2 The DIOGENES project is funded by a grant from the EU Food Quality and Safety Priority of the Sixth Framework Programme, contract no. FP6-2005-513946.
↵3 Current affiliation of KSV: MRC Centre for the Epidemiology of Child Health, UCL Institute of Child Health, London, United Kingdom.
↵4 Address correspondence and reprint requests to LH Larsen, Department of Human Nutrition, Faculty of Life Sciences, University of Copenhagen, Rolighedsvej 30, 1958 Frederiksberg C, Denmark. E-mail: [email protected].
Abstract
Background: Differences in the interindividual response to dietary intervention could be modified by genetic variation in nutrient-sensitive genes.
Objective: This study examined single nucleotide polymorphisms (SNPs) in presumed nutrient-sensitive candidate genes for obesity and obesity-related diseases for main and dietary interaction effects on weight, waist circumference, and fat mass regain over 6 mo.
Design: In total, 742 participants who had lost ≥8% of their initial body weight were randomly assigned to follow 1 of 5 different ad libitum diets with different glycemic indexes and contents of dietary protein. The SNP main and SNP-diet interaction effects were analyzed by using linear regression models, corrected for multiple testing by using Bonferroni correction and evaluated by using quantile-quantile (Q-Q) plots.
Results: After correction for multiple testing, none of the SNPs were significantly associated with weight, waist circumference, or fat mass regain. Q-Q plots showed that ALOX5AP rs4769873 showed a higher observed than predicted P value for the association with less waist circumference regain over 6 mo (−3.1 cm/allele; 95% CI: −4.6, −1.6; P/Bonferroni-corrected P = 0.000039/0.076), independently of diet. Additional associations were identified by using Q-Q plots for SNPs in ALOX5AP, TNF, and KCNJ11 for main effects; in LPL and TUB for glycemic index interaction effects on waist circumference regain; in GHRL, CCK, MLXIPL, and LEPR on weight; in PPARC1A, PCK2, ALOX5AP, PYY, and ADRB3 on waist circumference; and in PPARD, FABP1, PLAUR, and LPIN1 on fat mass regain for dietary protein interaction.
Conclusion: The observed effects of SNP-diet interactions on weight, waist, and fat mass regain suggest that genetic variation in nutrient-sensitive genes can modify the response to diet. This trial was registered at clinicaltrials.gov as NCT00390637.

Source: Am J Clin Nutr May 2012 vol. 95 no. 5 1254-1260

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