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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). 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.

SUBMITTER: Jacobo-Albavera L

PROVIDER: S-EPMC4647664 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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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.

Jacobo-Albavera Leonor L Posadas-Romero Carlos C Vargas-Alarcón Gilberto G Romero-Hidalgo Sandra S Posadas-Sánchez Rosalinda R González-Salazar María Del Carmen Mdel C Carnevale Alessandra A Canizales-Quinteros Samuel S Medina-Urrutia Aida A Antúnez-Argüelles Erika E Villarreal-Molina Teresa T

Nutrition & metabolism 20151116

<h4>Background</h4>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.<h4>Methods</h4>One thousand five hundred ...[more]

PMID: 26579206

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Project description:BackgroundABCA1 genetic variation is known to play a role in HDL-C levels and various studies have also implicated ABCA1 variation in cardiovascular risk. The functional ABCA1/R230C variant is frequent in the Mexican population and has been consistently associated with low HDL-C concentrations. Although it has been associated with other cardiovascular risk factors such as obesity and type 2 diabetes mellitus, it is not known whether it is associated with coronary artery disease (CAD).AimThe purpose of the study was to analyze whether the ABCA1/R230C variant is associated with premature CAD in a case-control association study (GEA or Genetics of Atherosclerotic Disease), and to explore whether BMI modulates the effect of the C230 allele on other metabolic traits using a population-based design.ResultsThe C230 allele was significantly associated with both lower HDL-C levels and a lower risk of premature CAD as compared to controls (OR?=?0.566; P(add)?=?1.499×10(-5)). In addition, BMI modulated the effect of R230C on body fat distribution, as the correlation between BMI and visceral to subcutaneous adipose tissue (a metric of the propensity to store fat viscerally as compared to subcutaneously) was negative in RR homozygous individuals, but positive in premenopausal women bearing the C230 allele, with a statistically significant interaction (P?=?0.005). BMI-R230C interaction was also significant for triglyceride levels in women regardless of their menopausal status (P?=?0.036).ConclusionThis is the first study assessing the effect of the R230C/ABCA1 variant in remature CAD. C230 was associated with both decreased HDL-C levels and a lower risk of premature CAD, and gender-specific BMI-R230C interactions were observed for different metabolic traits. These interactions may help explain inconsistencies in associations, and underscore the need to further analyze interactions of this functional and frequent variant with diet, exercise and other environmental factors.

Dataset Information

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.

Publications

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.

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