HDL and Epigenetics

The ratio of low density lipoprotein (LDL) to high density lipoprotein (HDL) is predictive of cardiovascular risk. Generally, a high LDL to HDL ratio is associated with an increase risk of cardiovascular disease. High density lipoprotein levels below <40 mg/dL are considered an independent risk factor for cardiovascular disease because they represent an increase in the likelihood of having a high LDL to HDL ratio. Low plasma HDL is common amongst Mexican adults, which may suggest a genetic component to variation in lipoprotein levels. However, environmental factors such as smoking, physical activity and diet are also known to affect levels, suggesting an epigenetic relationship. Alcohol intake has been well studied in relation to modification of the plasma concentrations of HDL. Evidence also suggests that diets dietary carbohydrate may play a role in modifying HDL concentrations, although tit is not clear if diet influences gene expression.

To clarify this issue, researchers used questionnaire data sampled from 3591 Mexican adults taking part in the a national survey, to investigate the association between HDL cholesterol and dietary factors, including carbohydrate intake. Data was adjusted for age, body mass index (BMI), smoking and alcohol consumption using linear regression, because these were known confounding variables for HDL modification. Using TaqMan assays, it was shown that the frequency of the ABCA1-R230C gene variant, that is associated with decreased HDL concentrations, was present in 9.3% of the subjects. This gene variant was significantly associated with low HDL concentrations in both sexes. The results also showed a significant inverse association between carbohydrate intake and HDL cholesterol concentration in women with the R230C gene variant and a significant diet gene interaction was found in postmenopausal women. Therefore in postmenopausal women the R230C gene is modulated by carbohydrate intake.

These results suggests that epigenetic factors may contribute to plasma HDL modification in humans. These results support previous studies showing that polymorphisms in the ABCA1 gene are associated with circulating concentrations of plasma HDL cholesterol in certain sub-populations. In particular, the ABCA1-R230C gene variant has been found to be particularly prevalent in the native Americans and Mexican populations. It has been estimated that the presence of this gene in the Mexican population may explain around 4% of the HDL cholesterol concentrations variation amongst this sub-population. This is much higher than the variation associated with a single nucleotide polymorphism identified in European and Asian populations. The ABCA1-R230C gene variant is thought to decrease cholesterol efflux by around 30 %, thus reducing plasma levels. The gender specific effects of the ABCA1-R230C gene may related to oestrogen’s ability to increase ABC transporter expression, postmenopausal women therefore having decreased efflux.


1Romero-Hidalgo, S. Villarreal-Molina, T., Gonzales-Barrios, J. A., Canizales-Quinteros, S., Rodriguez-Arellano, M. E., Yanez-Velazco, L. B., Bernal_alcantara, D. A., Villa, A. R., Antuna-Puente, B., Acufia-Alonzo, V., Merino-Garcia, J. L., Moreno-Sandoval, H. N. and Carnevale, A. 2012. Carbohydrate intake modulates the effects of the ABCA1-R230C variant on HDL cholesterol concentrations in postmenopausal women. Journal of Nutrition. 142: 278-283

About Robert Barrington

Robert Barrington is a writer, nutritionist, lecturer and philosopher.
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