Carbohydrate Intake Modulates the Effect of the ABCA1 -R230C Variant on HDL Cholesterol Concentrations in Premenopausal Women

Abstract

The R230C variant of the ATP-binding cassette transporter A1 (ABCA1) gene has been consistently associated with decreased HDL-cholesterol (HDL-C) concentrations in several studies in the Mexican mestizo population. However, information on how diet composition modifies the effect of the ABCA1-R230C variant on HDL-C concentrations is very scarce. The aim of the present study was to analyze whether the effect of ABCA1-R230C on HDL-C concentrations is modulated by dietary factors in a nationwide population sample of 3591 adults from the National Health and Nutrition Survey conducted by the State's Employees' Social Security and Social Services Institute. All participants answered a validated questionnaire to assess health status and weekly food consumption. Fasting blood samples were drawn for biochemical analysis and DNA extraction, and the ABCA1-R230C variant was genotyped using TaqMan assays. Statistical analyses consisted of simple linear and multiple regression modeling adjusting for age, BMI, smoking, and alcohol consumption. The overall C risk allele frequency was 9.3% and the variant was significantly associated with low HDL-C concentrations in both sexes. A significant negative correlation between carbohydrate consumption and HDL-C concentrations was observed in women bearing the R230C variant (P = 0.021) and a significant gene-diet interaction was found only in premenopausal women (P = 0.037). In conclusion, the effect of the ABCA1-R230C gene variant on HDL-C concentrations is modulated by carbohydrate intake in premenopausal women. This finding may help design optimized dietary interventions according to sex and ABCA1-R230C genotype.

The ABCA1 Gene R230C Variant Is Associated with Decreased Risk of Premature Coronary Artery Disease: The Genetics of Atherosclerotic Disease (GEA) Study

“…However other population-based studies have not found evidence of an increased risk of T2DM for C230 allele carriers [16], [17], including the present study. This may be due to differences in study design; however it is likely that diet, physical exercise, gender and other environmental factors may modify the effect of this functional allele on glucose and lipid metabolism, affecting the risk of T2DM.…”

“…The BMI-R230C interactions observed only in pre-menopausal women suggest that these effects may be estrogen-related. Several lines of evidence are consistent with this finding: ABCA1 -diet interactions affecting HDL-C levels have been reported in pre-menopausal women [17], improved lipid profiles have been observed in response to estrogen [42]–[43], and estrogen increased ABCA1 expression in different tissues in both mice and humans [44]–[46]. The increased risk of these metabolic parameters in pre-menopausal women is again in discrepancy with their risk of CAD, and whether this has to do with other systemic effects of estrogen, and/or with pleiotropic effects of the R230C variant in platelets, endothelium, inflammatory or other cell types remains to be elucidated.…”

“…To date, all reports assessing the effect of the ABCA1 /R230C variant on HDL-C concentrations including the present study have consistently shown highly significant associations with decreased HDL-C levels [13]–[17]. However, associations with other metabolic parameters such as obesity, T2DM and TG levels have been inconsistent.…”

“…In addition, the 230C allele has a functional effect decreasing cholesterol efflux by approximately 30% in vitro and shows evidence of positive selection in Native Americans [13]. This variant has been consistently associated with low HDL-C concentrations in various reports [13]–[17], and the sole presence of the C230 risk allele explains almost 4% of plasma HDL-C concentration variation, which is higher than all HDL-C variation associated with a single nucleotide polymorphism identified through genome-wide association studies in European and Asian populations [17]. Moreover, although it has been associated with additional cardiovascular risk factors such as increased body mass index (BMI), obesity, metabolic syndrome and type 2 diabetes mellitus (T2DM) [14], [18], it is not known whether it is associated with coronary artery disease (CAD).…”

Interaction between FTO rs9939609 and the Native American-origin ABCA1 rs9282541 affects BMI in the admixed Mexican population

“…Protocols and informed consent forms for each cohort were approved by their respective Institutional Ethics Committee as follows: Ethics Committee of the National Institute of Public Health [16]; IMSS Research Ethics Committee [17]; Biomedical Research in Humans of the Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán” (INCMNSZ) [2, 3]; Instituto Nacional de Cardiología “Ignacio Chávez” (INCICH) and the Ethics Committee of the Instituto Nacional de Medicina Genoómica (INMEGEN) [8]. Fully informed written consent for participation was attained from all participants or legal guardians.…”