The Link Between Genetics and Omega-3 (ELOVL2)

The ELOVL2 gene is responsible for the production of an enzyme called elongase, which elongates omega-3 and omega-6 fatty acids. For example, it's responsible for the extension of EPA (eicosapentaenoic acid) into DHA (docosahexaenoic acid) [R, R].

Both EPA and DHA are omega-3 polyunsaturated fatty acids (PUFAs), which are important for our health [R].

The ELOVL2 gene encodes an enzyme that elongates EPA into DHA.

One genome-wide association study (GWAS) looked at the genomes of over 1,000 Italians and 1,000 Americans. Scientists found that carrying an 'A' allele at rs953413, a SNP in ELOVL2, was associated with lower DHA levels and higher EPA levels [R].

A further study of over 300 participants from the UK found that carriers of minor alleles for several ELOVL2 SNPs all had lower baseline DHA than non-carriers [R]:

• rs3734398 ('C')
• rs2236212 ('C')
• rs953413 ('A')

Additionally, a study involving more than 3,500 Chinese and 9,000 European individuals confirmed the link between lower DHA and the 'C' allele of rs3734398, noting the risk allele to be more common in Chinese participants than European [R].

The effect of these SNPs on DHA levels is likely due to decreased levels of the enzyme coded by ELOVL2, which converts EPA into DHA [R].

ELOVL2 gene variants are associated with lower DHA levels, but increased EPA levels.

In a small Tunisian study, scientists compared 113 Alzheimer’s disease (AD) patients and 161 healthy people. They found that people with Alzheimer's had lower DHA levels. In addition, the 'TT' genotype for the rs3756963 SNP of the ELOVL2 gene was associated with an increased risk, while the 'CC' genotype was associated with decreased risk of Alzheimer's disease [R].

A further study of more than 200 chinese children with autism and more than 200 healthy controls found several ELOVL2 variants associated with risk of autism. The authors previously reported lower DHA levels in children with autism compared to controls. Carriers of two minor 'A' alleles at rs10498676 were at lower risk of autism, whilst carriers of both a major and minor allele at rs17606561, rs3756963, and rs9468304 were at a higher risk of autism [R].

ELOVL2 variants likely affect brain health by affecting the levels of DHA, and possibly other omega-3 and omega-6 fatty acids.

DHA is the most abundant omega-3 compound in the brain, and plays an important role in brain health, improving both mood and cognitive function [R, R, R].

For example, in one study with 280 middle-aged volunteers, higher blood DHA levels were associated with better reasoning and memory skills, higher vocabulary, and greater mental flexibility [R].

In another study with over 170 younger people, DHA supplementation has been associated with improved memory and reaction time [R].

There are also studies suggesting that low levels of omega-3 fatty acids — and the reduction of DHA in particular — may be associated with cognitive decline in the elderly. On the other hand, higher intake of omega-3s has been linked to a lower risk of dementia [R].

However, there are also studies that have reported no link between DHA and age-related cognitive decline [R, R, R].

Mice without the ELOVL2 gene have poorer memory and learning ability, as well as increased brain inflammation. These effects were reversed with dietary DHA [R].

ELOVL2 variants may affect brain function by affecting DHA levels. DHA is the most abundant fatty acid in the brain, and is important for optimal cognitive function.

ELOVL2 rs3734398:

• ‘TT’ = Associated with roughly average DHA levels [R]
• ‘CT’ = Associated with relatively decreased DHA levels [R]
• ‘CC’ = Associated with relatively decreased DHA levels [R]

Roughly 74% of people around the world carry at least one copy of the risk allele ‘C’. The risk allele is more common in East Asian populations, with more than 90% of individuals carrying it. On the other hand, 33% of Europeans and 57% of Africans have the beneficial 'TT' genotype [R].

ELOVL2  rs953413:

• ‘GG’ = Associated with roughly average DHA levels [R]
• ‘AG’ = Associated with relatively decreased DHA levels [R]
• ‘AA’ = Associated with relatively decreased DHA levels [R]

Roughly 87% of people carry the ‘A’ allele, while 13% have the no-risk 'GG' genotype. The beneficial 'GG' genotype is more common in Europeans, where 32% of people have it [R].

ELOVL2 rs2236212:

• ‘GG’ = Associated with roughly average DHA levels [R]
• ‘CG’ = Associated with relatively decreased DHA levels [R]
• ‘CC’ = Associated with relatively decreased DHA levels [R]

About 70% of people carry at least one 'C' risk allele, while 30% of people carry the beneficial 'GG' genotype. The 'GG' genotype is more common in Africans (63%) and Europeans (34%), but is rarely found in East Asians (6%) [R].