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

• Published in: The American journal of clinical nutrition 2012-05, Vol.95 (5), p.1254-1260
• Main Authors: LARSEN, Lesli H, ÄNGQUIST, Lars, MARTINEZ, J. Alfredo, PAPADAKI, Angeliki, PFEIFFER, Andreas Fh, VAN BAAK, Marleen A, SØRENSEN, Thorkild Ia, HOLST, Claus, LANGIN, Dominique, ASTRUP, Arne, SARIS, Wim Hm, VIMALESWARAN, Karani S, HAGER, Jörg, VIGUERIE, Nathalie, LOOS, Ruth Jf, HANDJIEVA-DARLENSKA, Teodora, JEBB, Susan A, KUNESOVA, Marie, LARSEN, Thomas M
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; Biological variation; Body fat; Body Mass Index; Body weight; Caloric Restriction; Caloric Restriction - methods; Cholecystokinin; Dietary Proteins; Dietary Proteins - administration & dosage; Diets; Diogenes; DNA; DNA - genetics; DNA - isolation & purification; Endocrinology and metabolism; Feeding Behavior; Feeding. Feeding behavior; Female; Food Habits; Fundamental and applied biological sciences. Psychology; Genes; Genetic diversity; Genetic Loci; Genotype; Glycemic Index; Glycemic Index - genetics; Human health and pathology; Humans; Life Sciences; Male; Middle Aged; Obesity; Obesity - genetics; Obesity - prevention & control; Peroxisome proliferator-activated receptors; Polymorphism; Polymorphism, Single Nucleotide; Polymorphism, Single Nucleotide - genetics; Protein interaction; Regression analysis; Single-nucleotide polymorphism; Tumor necrosis factor; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Waist Circumference; Weight; Weight Gain; Weight Gain - genetics; Weight Loss; Weight Loss - genetics
• ISSN: 0002-9165; 1938-3207
• DOI: 10.3945/ajcn.111.016543

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.