title: Dietary fat and carbohydrate modulate the effect of the ATP-binding cassette A1 (ABCA1) R230C variant on metabolic risk parameters in premenopausal women from the Genetics of Atherosclerotic Disease (GEA) Study.
abstract: BACKGROUND
  Although the R230C-ATP-binding cassette A1 (ABCA1) variant has been consistently associated with HDL-C levels, its association with diabetes and other metabolic parameters is unclear. Estrogen and dietary factors are known to regulate ABCA1 expression in different tissues. Thus, we aimed to explore whether gender, menopausal status and macronutrient proportions of diet modulate the effect of this variant on various metabolic parameters.
  
  
  METHODS
  One thousand five hundred ninety-eight controls from the GEA study were included (787 men, 363 premenopausal women and 448 menopausal women), previously assessed for anthropometric and biochemical measurements and visceral to subcutaneous abdominal fat (VAT/SAT) ratio on computed tomography. Taqman assays were performed for genotyping. Diet macronutrient proportions were assessed using a food frequency questionnaire validated for the Mexican population. Multivariate regression models were constructed to assess the interaction between the proportion of dietary macronutrients and the R230C polymorphism on metabolic parameters.
  
  
  RESULTS
  All significant interactions were observed in premenopausal women. Those carrying the risk allele and consuming higher carbohydrate/lower fat diets showed an unfavorable metabolic pattern [lower HDL-C and adiponectin levels, higher VAT/SAT ratio, homeostasis model assessment for insulin resistance (HOMA-IR) and higher gamma-glutamyl transpeptidase (GGT) and alkaline phosphatase (ALP) levels]. Conversely, premenopausal women carrying the risk allele and consuming lower carbohydrate/higher fat diets showed a more favorable metabolic pattern (higher HDL-C and adiponectin levels, and lower VAT/SAT ratio, HOMA-IR, GGT and ALP levels).
  
  
  CONCLUSIONS
  This is the first study reporting a gender-specific interaction between ABCA1/R230C variant and dietary carbohydrate and fat percentages affecting VAT/SAT ratio, GGT, ALP, adiponectin levels and HOMA index. Our study confirmed the previously reported gender-specific ABCA1-diet interaction affecting HDL-C levels observed in an independent study. Our results show how gene-environment interactions may help further understand how certain gene variants confer metabolic risk, and may provide information useful to design diet intervention studies.
authors.affiliation: Laboratorio de Genómica de Enfermedades Cardiovasculares, Instituto Nacional de Medicina Genómica, Mexico City, Mexico.
authors.forename: Leonor
authors.initials: L
authors.lastname: Jacobo-Albavera
authors.affiliation: Departamento de Endocrinología, Instituto Nacional de Cardiología "Ignacio Chávez", Mexico City, Mexico.
authors.forename: Carlos
authors.initials: C
authors.lastname: Posadas-Romero
authors.affiliation: Departamento de Biología Molecular, Instituto Nacional de Cardiología "Ignacio Chávez", Mexico City, Mexico.
authors.forename: Gilberto
authors.initials: G
authors.lastname: Vargas-Alarcón
authors.affiliation: Departamento de Genómica Computacional, Instituto Nacional de Medicina Genómica, Mexico City, Mexico.
authors.forename: Sandra
authors.initials: S
authors.lastname: Romero-Hidalgo
authors.affiliation: Departamento de Endocrinología, Instituto Nacional de Cardiología "Ignacio Chávez", Mexico City, Mexico.
authors.forename: Rosalinda
authors.initials: R
authors.lastname: Posadas-Sánchez
authors.affiliation: Departamento de Endocrinología, Instituto Nacional de Cardiología "Ignacio Chávez", Mexico City, Mexico.
authors.forename: María Del Carmen
authors.initials: Mdel C
authors.lastname: González-Salazar
authors.affiliation: Laboratorio de Enfermedades Mendelianas, Instituto Nacional de Medicina Genómica, Mexico City, Mexico.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Carnevale
authors.affiliation: Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química UNAM-INMEGEN, Mexico City, Mexico.
authors.forename: Samuel
authors.initials: S
authors.lastname: Canizales-Quinteros
authors.affiliation: Departamento de Endocrinología, Instituto Nacional de Cardiología "Ignacio Chávez", Mexico City, Mexico.
authors.forename: Aida
authors.initials: A
authors.lastname: Medina-Urrutia
authors.affiliation: Laboratorio de Genómica de Enfermedades Cardiovasculares, Instituto Nacional de Medicina Genómica, Periférico Sur 4809 Colonia Arenal Tepepan, CP 14610 México, D.F. Mexico.
authors.forename: Erika
authors.initials: E
authors.lastname: Antúnez-Argüelles
authors.affiliation: Laboratorio de Genómica de Enfermedades Cardiovasculares, Instituto Nacional de Medicina Genómica, Periférico Sur 4809 Colonia Arenal Tepepan, CP 14610 México, D.F. Mexico.
authors.forename: Teresa
authors.initials: T
authors.lastname: Villarreal-Molina
keywords: ABCA1; Adiponectin; GGT; Gene-diet interaction; HDL-C; Insulin resistance; R230C; Visceral to subcutaneous abdominal fat ratio