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Nutr Metab (Lond). 2015 Nov 16;12:45. doi: 10.1186/s12986-015-0040-3. eCollection 2015.

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.

Author information

1
Laboratorio de Genómica de Enfermedades Cardiovasculares, Instituto Nacional de Medicina Genómica, Mexico City, Mexico.
2
Departamento de Endocrinología, Instituto Nacional de Cardiología "Ignacio Chávez", Mexico City, Mexico.
3
Departamento de Biología Molecular, Instituto Nacional de Cardiología "Ignacio Chávez", Mexico City, Mexico.
4
Departamento de Genómica Computacional, Instituto Nacional de Medicina Genómica, Mexico City, Mexico.
5
Laboratorio de Enfermedades Mendelianas, Instituto Nacional de Medicina Genómica, Mexico City, Mexico.
6
Unidad de Genómica de Poblaciones Aplicada a la Salud, Facultad de Química UNAM-INMEGEN, Mexico City, Mexico.
7
Laboratorio de Genómica de Enfermedades Cardiovasculares, Instituto Nacional de Medicina Genómica, Periférico Sur 4809 Colonia Arenal Tepepan, CP 14610 México, D.F. Mexico.

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).

CONCLUSION:

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.

KEYWORDS:

ABCA1; Adiponectin; GGT; Gene-diet interaction; HDL-C; Insulin resistance; R230C; Visceral to subcutaneous abdominal fat ratio

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