title: Modulation by dietary fat and carbohydrate of IRS1 association with type 2 diabetes traits in two populations of different ancestries.
abstract: OBJECTIVE
  Insulin receptor substrate 1 (IRS1) is central to insulin signaling pathways. This study aimed to examine the association of IRS1 variants with insulin resistance (IR) and related phenotypes, as well as potential modification by diet.
  
  
  METHODS
  Two IRS1 variants (rs7578326 and rs2943641) identified by genome-wide association studies as related to type 2 diabetes were tested for their associations with IR and related traits and interaction with diet in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study (n = 820) and the Boston Puerto Rican Health Study (BPRHS) (n = 844).
  
  
  RESULTS
  Meta-analysis indicated that rs7578326 G-allele carriers and rs2943641 T-allele carriers had a lower risk of IR, type 2 diabetes, and metabolic syndrome (MetS). Significant interactions on IR and MetS were found for these two variants and their haplotypes with diet. In GOLDN, rs7578326 G-allele carriers and rs2943641 T-allele carriers and their haplotype G-T carriers had a significantly lower risk of IR and MetS than noncarriers only when the dietary saturated fatty acid-to-carbohydrate ratio was low (≤ 0.24). In both GOLDN (P = 0.0008) and BPRHS (P = 0.011), rs7578326 G-allele carriers had a lower risk of MetS than noncarriers only when dietary monounsaturated fatty acids were lower than the median intake of each population.
  
  
  CONCLUSIONS
  IRS1 variants are associated with IR and related traits and are modulated by diet in two populations of different ancestries. These findings suggest that IRS1 variants have important functions in various metabolic disorders and that dietary factors could modify these associations.
authors.affiliation: Department of Food Science and Nutrition, Zhejiang University, Hangzhou, China.
authors.forename: Ju-Sheng
authors.initials: JS
authors.lastname: Zheng
authors.forename: Donna K
authors.initials: DK
authors.lastname: Arnett
authors.forename: Laurence D
authors.initials: LD
authors.lastname: Parnell
authors.forename: Caren E
authors.initials: CE
authors.lastname: Smith
authors.forename: Duo
authors.initials: D
authors.lastname: Li
authors.forename: Ingrid B
authors.initials: IB
authors.lastname: Borecki
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Tucker
authors.forename: José M
authors.initials: JM
authors.lastname: Ordovás
authors.forename: Chao-Qiang
authors.initials: CQ
authors.lastname: Lai
mesh_terms: D000328:Adult; D000483:Alleles; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics*; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology; D008297:Male; D008875:Middle Aged
chemical_list: D004040:Dietary Carbohydrates; D004041:Dietary Fats; D055504:Insulin Receptor Substrate Proteins