title: IRS1 genotype modulates metabolic syndrome reversion in response to 2-year weight-loss diet intervention: the POUNDS LOST trial.
abstract: OBJECTIVE
  Genetic variants near IRS1 are associated with features of the metabolic syndrome (MetS). We examined whether genetic variants near IRS1 might modulate the effects of diets varying in fat content on the MetS status in a 2-year weight-loss trial.
  
  
  METHODS
  Two variants near IRS1, rs1522813 and rs2943641, were genotyped in 738 overweight/obese adults (age 60 ± 9 years; BMI 32.7 ± 3.9 kg/m2) randomly assigned to one of four weight-loss diets (a deficit of 750 kcal/day of caloric intake from baseline) varying in macronutrient contents for 2 years. We compared MetS status of high-fat (40% of caloric intake; n = 370) and low-fat (20% caloric intake; n = 368) diet groups differentiated by genotypes (rs1522813 A-allele carriers and noncarriers and rs2943641T-allele carriers and noncarriers).
  
  
  RESULTS
  Among rs1522813 A-allele carriers, the reversion rates of the MetS were higher in the high-fat diet group than those in the low-fat diet group over the 2-year intervention (P = 0.002), while no significant difference between diet groups was observed among noncarriers (P = 0.27). The genetic modulation on dietary effect was independent of weight changes. The odds ratio (OR) for the 2-year reversion of the MetS was 2.88 (95% CI 1.25-6.67) comparing the high-fat and low-fat diets among rs1522813 A-allele carriers, while the corresponding OR was 0.83 (0.36-1.92) in noncarriers. The variant rs2943641 was not observed to modulate dietary effects on the MetS status.
  
  
  CONCLUSIONS
  Our data suggest that high-fat weight-loss diets might be more effective in the management of the MetS compared with low-fat diets among individuals with the A-allele of the rs1522813 variant near IRS1.
authors.affiliation: Corresponding author: Lu Qi, nhlqi@channing.harvard.edu.
authors.forename: Qibin
authors.initials: Q
authors.lastname: Qi
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.forename: Hongyu
authors.initials: H
authors.lastname: Wu
authors.forename: Liming
authors.initials: L
authors.lastname: Liang
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Champagne
authors.forename: George A
authors.initials: GA
authors.lastname: Bray
authors.forename: Frank M
authors.initials: FM
authors.lastname: Sacks
authors.forename: Lu
authors.initials: L
authors.lastname: Qi
mesh_terms: D000328:Adult; D000483:Alleles; D018752:Diet, Fat-Restricted; D059305:Diet, High-Fat / Q000009:adverse effects; D004038:Diet, Reducing; D002149:Energy Intake; D005260:Female; D005838:Genotype; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics*; D008297:Male; D024821:Metabolic Syndrome / Q000178:diet therapy* / Q000235:genetics*; D008875:Middle Aged; D009765:Obesity / Q000178:diet therapy; D050177:Overweight / Q000178:diet therapy; D015431:Weight Loss / Q000235:genetics
chemical_list: C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins