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

• DOI: 10.3945/ajcn.111.016543
• Publication Date: 2012-04-06T00:50:03Z
• Authors: Lesli H Larsen; Lars Ängquist; Karani S Vimalesw...; Jörg Hager; Nathalie Viguerie; Ruth JF Loos; Teodora Handjieva...; Susan A Jebb; Marie Kunešova; Thomas M Larsen; J Alfredo Martinez; Angeliki Papadaki; Andreas FH Pfeiffer; Marleen A van Baak; Thorkild IA Sørensen; Claus Holst; Dominique Langin; Arne Astrup; Wim HM Saris
• Keywords: Male; MESH: Dietary Proteins; BEHAVIOR INTERACTIONS; PROTEIN; MESH: Food Habits; Weight Gain; Body Mass Index; MESH: Genotype; 0302 clinical medicine; MESH: Obesity; [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism; 2. Zero hunger; MESH: Middle Aged; MESH: Polymorphism, Single Nucleotide; MESH: DNA; [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism; Middle Aged; MESH: Waist Circumference; OBESITY; MESH: Weight Gain; DIETS; Female; Dietary Proteins; Waist Circumference; Adult; Genotype; 610; LOSS MAINTENANCE; MESH: Genetic Loci; Polymorphism, Single Nucleotide; MESH: Body Mass Index; MESH: Weight Loss; 03 medical and health sciences; Weight Loss; Humans; Obesity; Caloric Restriction; MESH: Caloric Restriction; MESH: Humans; MESH: Adult; DNA; Feeding Behavior; MESH: Male; Genetic Loci; Glycemic Index; MESH: Glycemic Index; GLYCEMIC INDEX; MESH: Female

Differences in the interindividual response to dietary intervention could be modified by genetic variation in nutrient-sensitive genes.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.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.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.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.