title: Interaction of an S100A9 gene variant with saturated fat and carbohydrates to modulate insulin resistance in 3 populations of different ancestries.
abstract: BACKGROUND
  S100 calcium-binding protein A9 (S100A9) has previously been identified as a type 2 diabetes (T2D) gene. However, this finding requires independent validation and more in-depth analyses in other populations and ancestries.
  
  
  OBJECTIVE
  We aimed to replicate the associations between an S100A9 variant and insulin resistance and T2D and to initiate an investigation of potential interactions with the habitual diet in several independent populations.
  
  
  METHODS
  We investigated the association of the S100A9 variant rs3014866 with insulin resistance and T2D risk and its interactions with diet in 3 diverse populations as follows: the CORDIOPREV (Coronary Diet Intervention with Olive Oil and Cardiovascular Prevention; n = 711), which consisted of Spanish white adults; the GOLDN (Genetics of Lipids Lowering Drugs and Diet Network; n = 818), which involved North American non-Hispanic white adults; and Hispanic adults who participated in the BPRHS (Boston Puerto Rican Health Study; n = 1155).
  
  
  RESULTS
  Meta-analysis indicated that T carriers presented a lower risk of T2D than CC carriers (pooled OR: 0.714; 95% CI: 0.584, 0.845; P = 0.002). In all 3 populations (CORDIOPREV, GOLDN, and BPRHS), we showed a significant interaction between the rs3014866 single nucleotide polymorphism and dietary SFA:carbohydrate ratio intake for the homeostasis model assessment of insulin resistance (HOMA-IR) (P = 0.028, P = 0.017, and P = 0.026, respectively). CC carriers had a significantly higher HOMA-IR only when SFA:carbohydrate intake was high (P = 0.045 for the CORDIOPREV, P = 0.033 for the GOLDN, and P = 0.046 for the BPRHS) but not when SFA:carbohydrate ratio intake was low.
  
  
  CONCLUSIONS
  The minor allele (T) of the S100A9 variant rs3014866 is associated with lower T2D risk in 3 populations of different ancestries. Note that individuals with the high-risk CC genotype may be more likely to benefit from a low SFA:carbohydrate ratio intake to improve insulin resistance as evaluated with the use of the HOMA-IR. These trials were registered at clinicaltrials.gov as NCT00924937 (CORDIOPREV), NCT00083369 (GOLDN), and NCT01231958 (BPRHS).
authors.affiliation: Lipids and Atherosclerosis Unit, Reina Sofia University Hospital, Maimonides Institute for Biomedical Research at Cordoba, University of Cordoba, Cordoba, Spain; Centro de Investigación Biomédica en Red (CIBER) Fisiopatologia Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain; Nutrition and Genomics Laboratory and.
authors.forename: Ruth
authors.initials: R
authors.lastname: Blanco-Rojo
authors.affiliation: Lipids and Atherosclerosis Unit, Reina Sofia University Hospital, Maimonides Institute for Biomedical Research at Cordoba, University of Cordoba, Cordoba, Spain; Centro de Investigación Biomédica en Red (CIBER) Fisiopatologia Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain;
authors.forename: Javier
authors.initials: J
authors.lastname: Delgado-Lista
authors.affiliation: Nutrition and Genomics Laboratory and.
authors.forename: Yu-Chi
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Agricultural Research Service, USDA, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA;
authors.forename: Chao-Qiang
authors.initials: CQ
authors.lastname: Lai
authors.affiliation: Lipids and Atherosclerosis Unit, Reina Sofia University Hospital, Maimonides Institute for Biomedical Research at Cordoba, University of Cordoba, Cordoba, Spain; Centro de Investigación Biomédica en Red (CIBER) Fisiopatologia Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain;
authors.forename: Pablo
authors.initials: P
authors.lastname: Perez-Martinez
authors.affiliation: Lipids and Atherosclerosis Unit, Reina Sofia University Hospital, Maimonides Institute for Biomedical Research at Cordoba, University of Cordoba, Cordoba, Spain; Centro de Investigación Biomédica en Red (CIBER) Fisiopatologia Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain;
authors.forename: Oriol
authors.initials: O
authors.lastname: Rangel-Zuñiga
authors.affiliation: Nutrition and Genomics Laboratory and.
authors.forename: Caren E
authors.initials: CE
authors.lastname: Smith
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL;
authors.forename: Bertha
authors.initials: B
authors.lastname: Hidalgo
authors.affiliation: Lipids and Atherosclerosis Unit, Reina Sofia University Hospital, Maimonides Institute for Biomedical Research at Cordoba, University of Cordoba, Cordoba, Spain; Centro de Investigación Biomédica en Red (CIBER) Fisiopatologia Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain;
authors.forename: Juan F
authors.initials: JF
authors.lastname: Alcala-Diaz
authors.affiliation: Lipids and Atherosclerosis Unit, Reina Sofia University Hospital, Maimonides Institute for Biomedical Research at Cordoba, University of Cordoba, Cordoba, Spain; Centro de Investigación Biomédica en Red (CIBER) Fisiopatologia Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain;
authors.forename: Francisco
authors.initials: F
authors.lastname: Gomez-Delgado
authors.affiliation: Agricultural Research Service, USDA, Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA;
authors.forename: Laurence D
authors.initials: LD
authors.lastname: Parnell
authors.affiliation: Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL;
authors.forename: Donna K
authors.initials: DK
authors.lastname: Arnett
authors.affiliation: Department of Clinical Laboratory and Nutritional Sciences, University of Massachusetts, Lowell, MA;
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Tucker
authors.affiliation: Lipids and Atherosclerosis Unit, Reina Sofia University Hospital, Maimonides Institute for Biomedical Research at Cordoba, University of Cordoba, Cordoba, Spain; Centro de Investigación Biomédica en Red (CIBER) Fisiopatologia Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain; jose.ordovas@tufts.edu.
authors.forename: Jose
authors.initials: J
authors.lastname: Lopez-Miranda
authors.affiliation: Nutrition and Genomics Laboratory and Department of Epidemiology, Spanish National Center for Cardiovascular Research (CNIC), Madrid, Spain; and Madrid Institute for Advanced Studies (IMDEA) Food Institute, Madrid, Spain jose.ordovas@tufts.edu.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Ordovas
mesh_terms: D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000235:genetics*; D004032:Diet; D004040:Dietary Carbohydrates / Q000009:adverse effects*; D004041:Dietary Fats / Q000009:adverse effects*; D005247:Feeding Behavior; D005260:Female; D059647:Gene-Environment Interaction; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D009418:S100 Proteins / Q000235:genetics*
chemical_list: D004040:Dietary Carbohydrates; D004041:Dietary Fats; D009418:S100 Proteins
keywords: SFA:carbohydrate ratio; S100A9 gene; gene-diet interaction; insulin resistance; type 2 diabetes