title: Analyses of single nucleotide polymorphisms in selected nutrient-sensitive genes in weight-regain prevention: the DIOGENES study.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Human Nutrition, LIFE, University of Copenhagen, Copenhagen, Denmark. lehla@life.ku.dk
authors.forename: Lesli H
authors.initials: LH
authors.lastname: Larsen
authors.forename: Lars
authors.initials: L
authors.lastname: Angquist
authors.forename: Karani S
authors.initials: KS
authors.lastname: Vimaleswaran
authors.forename: Jörg
authors.initials: J
authors.lastname: Hager
authors.forename: Nathalie
authors.initials: N
authors.lastname: Viguerie
authors.forename: Ruth J F
authors.initials: RJ
authors.lastname: Loos
authors.forename: Teodora
authors.initials: T
authors.lastname: Handjieva-Darlenska
authors.forename: Susan A
authors.initials: SA
authors.lastname: Jebb
authors.forename: Marie
authors.initials: M
authors.lastname: Kunesova
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Larsen
authors.forename: J Alfredo
authors.initials: JA
authors.lastname: Martinez
authors.forename: Angeliki
authors.initials: A
authors.lastname: Papadaki
authors.forename: Andreas F H
authors.initials: AF
authors.lastname: Pfeiffer
authors.forename: Marleen A
authors.initials: MA
authors.lastname: van Baak
authors.forename: Thorkild Ia
authors.initials: TIa
authors.lastname: Sørensen
authors.forename: Claus
authors.initials: C
authors.lastname: Holst
authors.forename: Dominique
authors.initials: D
authors.lastname: Langin
authors.forename: Arne
authors.initials: A
authors.lastname: Astrup
authors.forename: Wim H M
authors.initials: WH
authors.lastname: Saris
mesh_terms: D000328:Adult; D015992:Body Mass Index; D031204:Caloric Restriction / Q000379:methods; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004044:Dietary Proteins / Q000008:administration & dosage; D005247:Feeding Behavior; D005260:Female; D056426:Genetic Loci; D005838:Genotype; D038321:Glycemic Index / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics / Q000517:prevention & control*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D055105:Waist Circumference; D015430:Weight Gain / Q000235:genetics*; D015431:Weight Loss / Q000235:genetics
chemical_list: D004044:Dietary Proteins; D004247:DNA