ABCA1

Protein:

ATP Binding Cassette SAM1

SNP ID:

G66+1594A
R230C

The ATP-binding cassette family of genes encodes for membrane proteins that function as shuttles. ATP Binding Cassette SAM1 (ABCA1) is one such protein which acts as a cholesterol pump and is encoded for by the gene ABCA1. ABCA1 is responsible for shuttling cholesterol and other fats called phospholipids out of cells into the blood where they can bind with apolipoproteins to form high-density lipoproteins (HDL), sometimes termed “good” cholesterol. These HDL particles are typically shuttled to the liver for further processing or to be excreted from the body 1.

ABCA1 plays a crucial role in the maintenance of cholesterol metabolism in the body. This is highlighted by a very rare disease that’s caused due to a mutation of the ABCA1 gene, called Tangier disease. The disease is characterized by low circulating levels of HDL-cholesterol (HDL-C) levels in the body, higher levels of fat in the blood, impaired nerve functionality, and enlarged orange-colored tonsils. These individuals have a higher risk of cardiovascular disease and deposition of fat in the soft tissues, leading to impaired health.

See: Cholesterol and heart health: What you need to know

There are two SNPs in the ABCA1 gene associated with poor health outcomes. One SNP, G66+1594A, has a particularly strong association with age-related macular degeneration (AMD). The second SNP, R230C, is associated with increased cardiovascular risk in Mexican Mestizos and Native American populations.

G66+1594A

Science Grade :

B+

Longevity

rsID Number	Major Allele	Minor Allele	Minor Allele Frequency (%)
rs1883025	g	a	26

Risk Description

The risk ‘A’ allele of G66+1594A in the ABCA1 gene is associated with an increased risk of developing age-related macular degeneration (AMD), which can lead to a loss of vision, especially central vision. AMD is characterized by the development of inflammation and oxidative stress in the macula part of the retina at the back of the eye which leads to damage of this delicate tissue.

It has been hypothesized that the ‘A’ allele of G66+1594A leads to reduced ABCA1 function. This reduction in function means that rather than cholesterol being secreted out of cells in the macula into the bloodstream it instead accumulates within the macular cells. This accumulated cholesterol is at risk of peroxidation leading to the release of damaging reactive oxygen species or free radicals. These free radicals damage the tissue of the retina leading to a progressive loss of vision 2.

Indirect Nutrients:^*

Ingredient	Active Ingredient	Effect
Lutein		Lutein is one of over 600 naturally occurring compounds known as carotenoids. These natural pigments are produced by plants to absorb energy from light for use in photosynthesis, whilst also protecting the plant from damage from excessive light 3. Animals are incapable of synthesizing lutein and so must acquire it from their diet, with dark green plants such as spinach or kale being particularly rich sources. Lutein accumulates in the retina of the eye and is thought to protect the sensitive tissue from damage, whilst also acting as an antioxidant 4. In those carrying the ‘A’ allele of G66+1594A who are at risk of free radicals being produced in the macula leading to the development of AMD lutein may serve two purposes. To protect against free radical oxidative damage, and to protect against further damage from exposure to light 5.
Zeaxanthin		Zeaxanthin is one of the most common naturally occurring compounds known as carotenoids. These natural plant pigments absorb energy from light for use in photosynthesis, whilst also protecting the plant from damage from excessive light 4. Animals cannot synthesize zeaxanthin and so must acquire it from their diet, with reddy vegetables and spices such as paprika or saffron being rich sources. Zeaxanthin accumulates in the macula of the retina at the back of the eye and is thought to protect the sensitive tissue from damage, whilst also acting as an antioxidant 6. In those carrying the ‘A’ allele of G66+1594A who are at risk of free radicals being produced in the macula leading to the development of AMD, and a loss of vision, zeaxanthin may serve two purposes. To protect against free radical oxidative damage, and to protect against further damage from exposure to light 7.
Vitamin C	Ascorbic acid	Vitamin C is a potent antioxidant which can protect against oxidative stress induced by free radicals 8. Those carrying the ‘A’ allele of G66+1594A, are at risk of free radicals being produced as a result of cholesterol accumulation in the macula leading to the development of AMD, and a loss of vision. As an antioxidant vitamin C is well placed to prevent damage to the delicate tissue of the retina and prevent or delay the onset of AMD 7.
Vitamin E	α-tocopherol	As with vitamin C above vitamin E is a potent antioxidant 9, especially for lipid derived free radicals. For those carrying the ‘A’ allele of G66+1594A, who are at risk of free radical driven AMD, getting adequate vitamin E may be beneficial 7.
Omega-3 fatty acids	EPA, DHA, ALA	Omega-3 fatty acids are known to fight inflammation, and also against the accumulation of ‘bad’ cholesterol or LDL-cholesterol. Since AMD is characterized by the accumulation of cholesterol or lipid deposits within the macula, omega-3 fatty acids may help improve the disease prognosis 10. These polyunsaturated fatty acids bind to the cell membrane receptors and modify their function. Omega-3 fatty acids may therefore modify the function of ABCA1 transporters in those with the ‘A’ allele of G66+1594A genes.

Discuss this information with your doctor before taking any course of action.

Citations:

R230C

Science Grade :

Longevity

rsID Number	Major Allele	Minor Allele	Minor Allele Frequency (%)	Major Amino Acid	Minor Amino Acid
rs9282541	g	a	10	Arg	Cys

Risk Description

R230C is a functional SNP that lowers plasma levels of circulating HDL-cholesterol in Mexican populations, especially in premenopausal women11. Those with the risk allele ‘A’ have poor metabolic outcomes, since cholesterol builds up within cells and can no longer be delivered to the liver for metabolization.

The gene-diet interactions are particularly strong here since the high-carb diet that’s a staple to Mexican cuisine is inversely correlated to plasma HDL-cholesterol levels12. A diet that takes into account the lowered cholesterol efflux capacity of the ABCA1 transporter protein can help those with the risk allele lead a nutritious, healthy life with a normal metabolism.

Given these risk variants, nutrition that’s tailored to the specific region and local food tradition, supplemented by a higher protein diet, could help in better metabolic outcomes. A research publication that studied the effect of a dietary treatment for such hyperlipidemic patients shows promise for increasing plasma levels of HDL-cholesterol in R230C individuals13.

Recommended Dietary Food

Food	Effect
LSF-SF (Low Saturated Fat- Soy protein and Soluble Fiber) Diet	Soy protein builds muscle, contains all the essential amino acids required in one’s dietary intake, and lowers ‘bad’ cholesterol. It is therefore the immediate choice of diet for those who have dietary restrictions that preclude them from taking high-fat or high-carb diets. Those with the R230C risk allele responded to a recommended diet of a soy protein and soluble fiber with increased plasma levels of circulating HDL-cholesterol.
Low Glycemic-Index Foods	Foods that are less starchy, such as oats, bulgur and non-starchy vegetables, help diversify the calorific intake of those with the R230C allele from a protein-rich or soy-rich diet. As these foods have very low starch content, they will not require cholesterol shuttling, and will therefore not tax the metabolism capabilities of those with the R230C allele.

Discuss this information with your doctor before taking any course of action.

Risk Description

Indirect Nutrients:*

Citations:

Risk Description

Citations:

Indirect Nutrients:^*