Can This Gene Affect Vitamin B12 Levels? (FUT2)

The FUT2 gene helps create an enzyme called galactoside 2-alpha-L-fucosyltransferase 2 [R]. 

This enzyme is involved in several chemical reactions in the body, including the production of the H antigen [R].

The H antigen acts as a precursor to the ABO blood group antigens, which determine a person’s blood type [R].

Research suggests that certain genetic variations in FUT2 may influence health, such as increasing the risk for infections and altering how the body absorbs vitamins, especially vitamin B12 [R, R].

The FUT2 gene helps create an enzyme that plays a key role in determining blood type. Variations in FUT2 have been linked to health disorders and altered vitamin absorption.

Vitamin B12 (also called cobalamin) is an essential nutrient that the body needs in order to function properly [R].

This vitamin plays an important role in many biological processes, some of which include [R]:

• Production of DNA
• Development of red blood cells
• Development of the nervous system
• Cell metabolism

Vitamin B12 primarily works by acting as a coenzyme, a substance that interacts with enzymes to facilitate chemical reactions [R].

Most people get most of the vitamin B12 they need from their diet. We’ll talk more about the sources of vitamin B12 later on in the article.

Vitamin B12 Deficiency

Vitamin B12 deficiency occurs when the body does not get enough of the vitamin. If you suspect you may have a vitamin B12 deficiency, speak with your doctor.

Some symptoms of vitamin B12 deficiency include [R]:

• Tiredness
• Weakness
• Constipation
• Loss of appetite
• Weight loss
• Numbness/tingling in the hands and feet

Some groups may be more at risk for deficiency, such as [R]:

• Older adults (due to reduced stomach acid production)
• People with gastrointestinal disorders
• People who have had gastrointestinal surgery
• Vegetarians (plant-based foods typically do not contain vitamin B12)

In addition, certain medications may reduce vitamin B12 levels, including [R]:

• H2 receptor antagonists, such as famotidine (Pepcid) and ranitidine (Zantac)
• Proton pump inhibitors, such as omeprazole (Prilosec) and lansoprazole (Prevacid)
• Metformin, a common diabetes medication

Vitamin B12 Absorption

Before we discuss how FUT2 may affect vitamin B12 levels, we first have to talk about how the body absorbs this vitamin.

The absorption process of vitamin B12 is fairly complex. The following outlines the general steps [R]:

1. Stomach acid separates vitamin B12 that is attached to food proteins
2. Intrinsic factor (IF), a protein secreted by stomach cells, attaches to vitamin B12
3. This IF/vitamin B12 complex is transported and absorbed through the gut

Any condition that disrupts this process can impair the absorption of vitamin B12.

For example, stomach acid production naturally decreases with age, which can reduce the body’s ability to separate vitamin B12 from food [R].

This is why older adults are at a higher risk of vitamin B12 deficiency [R].

How FUT2 Variants Affect Vitamin B12 Levels

It’s not entirely clear how variants of the FUT2 gene lead to low vitamin B12 levels. According to research, it is likely due to impaired absorption.

One theory is that FUT2 variants called secretors may increase the risk of H. pylori infection, which in turn impairs vitamin B12 absorption [R].

Let’s break this down. Certain variants in FUT2 are called secretors because they produce active enzymes that secrete antigens into bodily fluids [R].

Researchers have found that people with this secretor variant are more susceptible to certain infections, including H. pylori (a type of bacteria that commonly infects the stomach) [R, R].

An H. pylori infection can reduce stomach acid production and lower levels of intrinsic factor, which can impair the absorption of vitamin B12 [R].

The evidence is not clear-cut, however. Some studies suggest that H. pylori infection status has no effect on the association between FUT2 and vitamin B12 levels [R].

Certain FUT2 variants are associated with H. pylori infection. This infection can impair the absorption of vitamin B12, which may explain why certain FUT2 variants are associated with low vitamin B12 levels.

Who Is At Risk?

Studies show that certain genetic variants of FUT2 called ‘secretors’ are linked to lower vitamin B12 levels.

On the other hand, variants that lead to less active enzymes (called non-secretors) are associated with higher vitamin B12 levels.

The rs602662 SNP

One example of a secretor variant is the ‘GG’ genotype in rs602662 [R].

A study of 1,100 people from an Indian population found that the ‘GG’ genotype in rs602662 was associated with significantly lower vitamin B12 levels compared to other genotypes [R].

Another genome-wide study looking at populations from Italy and the U.S. (Baltimore area) shows the same link between the ‘GG’ genotype and low vitamin B12 [R].

According to the same studies, those with the heterozygous ‘GA’ genotype had intermediate levels of vitamin B12 [R].

The ‘GG’ genotype in rs602662 is associated with low vitamin B12 levels in Italian, American, and Indian populations.

The rs492602 SNP

One genome-wide study examined the rs492602 SNP in over 2,700 women [R].

The researchers found that the ‘GG’ genotype (a non-secretor variant) was linked to higher vitamin B12 levels in women compared to the ‘AA’ secretor genotype [R].

Individuals with the heterozygous ‘AG’ genotype appear to have intermediate vitamin B12 levels [R].

The ‘GG’ genotype in rs492602 is linked to higher vitamin B12 levels in women.

The rs601338 SNP

A study looked at the rs601338 SNP of FUT2 in over 1,200 people from Europe and West Africa [R].

According to the study, those with the ‘AA’ genotype (the non-secretor variant) have significantly higher vitamin B12 levels compared to those with other genotypes [R].

Similar to the other SNPs, those with the heterozygous genotype had intermediate levels of vitamin B12 [R]. 

People with the ‘AA’ genotype in rs601338 may have higher vitamin B12 levels, according to research of European and West African populations.

You can see your genotypes for FUT2 in the table below. However, keep in mind that these associations are based on studies from certain ethnic populations — so you should interpret your results with caution if you are not descended from one of these specific groups!

Primary SNPs: 

FUT2 rs602662

• ‘GG’ (secretor variant) = Associated with lower vitamin B12 levels
• ‘GA’ = Associated with intermediate vitamin B12 levels
• ‘AA’ (non-secretor variant) = Associated with higher vitamin B12 levels
• This association has only been found in Italian, American, and Indian populations

FUT2 rs492602

• ‘AA’ (secretor variant) = Associated with lower vitamin B12 levels
• ‘AG’ = Associated with intermediate vitamin B12 levels
• ‘GG’ (non-secretor variant) = Associated with higher vitamin B12 levels
• This association has only been found in women

FUT2 rs601338

• ‘GG’ (secretor variant) = Associated with lower vitamin B12 levels
• ‘GA’ = Associated with intermediate vitamin B12 levels
• ‘AA’ (non-secretor variant) = Associated with higher vitamin B12 levels
• This association has only been found in European and West African populations

Population Frequencies

These three SNPs (rs602662, rs492602, rs601338) are often inherited together.

For example, if an individual has a non-secretor variant in rs602662, they likely also have the non-secretor variant in rs492602 and rs601338.

This means if a person has one variant associated with high vitamin B12 levels, their other variants are also likely linked to higher vitamin B12.

Generally speaking, the secretor alleles are more common than the non-secretor alleles.

In European populations, roughly 30% of people have the homozygous secretor genotype and about 20% have the non-secretor genotype.

In East Asian populations, about 99% of people have the homozygous secretor genotype while less than 1% have the non-secretor genotype.