Analyses of single nucleotide polymorphisms in selected nutrientsensitive genes in weight-regain prevention: The DIOGENES study
Larsen LH., Ängquist L., Vimaleswaran KS., Hager J., Viguerie N., Loos RJF., Handjieva-Darlenska T., Jebb SA., Kunešova M., Larsen TM., Martinez JA., Papadaki A., Pfeiffer AFH., Van Baak MA., Sørensen TIA., Holst C., Langin D., Astrup A., Saris WHM.
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 (23.1 cm/allele; 95% CI: 24.6, 21.6; 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 nutrientsensitive genes can modify the response to diet. This trial was registered at clinicaltrials.gov as NCT00390637. © 2012 American Society for Nutrition.