Analyses of single nucleotide polymorphisms in selected nutrient-sensitive genes in weight-regain prevention: the DIOGENES study

Lesli H Larsen, Lars Angquist, Karani S Vimaleswaran, Jörg Hager, Nathalie Viguerie, Ruth J F Loos, Teodora Handjieva-Darlenska, Susan A Jebb, Marie Kunesova, Thomas M Larsen, J Alfredo Martinez, Angeliki Papadaki, Andreas F H Pfeiffer, Marleen A van Baak, Thorkild Sorensen, Claus Holst, Dominique Langin, Arne Astrup, Wim H M Saris

Research output: Contribution to journalArticle (Academic Journal)

26 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)1254-60
Number of pages7
JournalAmerican Journal of Clinical Nutrition
Volume95
Issue number5
DOIs
Publication statusPublished - 2012

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  • Cite this

    Larsen, L. H., Angquist, L., Vimaleswaran, K. S., Hager, J., Viguerie, N., Loos, R. J. F., Handjieva-Darlenska, T., Jebb, S. A., Kunesova, M., Larsen, T. M., Martinez, J. A., Papadaki, A., Pfeiffer, A. F. H., van Baak, M. A., Sorensen, T., Holst, C., Langin, D., Astrup, A., & Saris, W. H. M. (2012). Analyses of single nucleotide polymorphisms in selected nutrient-sensitive genes in weight-regain prevention: the DIOGENES study. American Journal of Clinical Nutrition, 95(5), 1254-60. https://doi.org/10.3945/ajcn.111.016543