When Was MTHFR Gene Discovered?

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Hi everyone,

I have an interesting subject for you today as I’m going to elaborate on:

When Was MTHFR Gene First Discovered…

I don’t know about you, but I love to look up and learn as much as possible about the MTHFR gene and its background.

Somehow it feels logical…

The only way to truly understand its importance you need to know as much as possible about a gene variation you carry.

A while ago, I got curious about the history of the MTHFR gene, and you’re going to learn more about it, too, in this post.

When Was MTHFR Gene First Discovered

Beginnings of MTHFR history

The discovery of methylenetetrahydrofolate reductase (MTHFR) is a complicated subject, for sure.

Saying it was discovered in a specific year is too confusing because of the whole chain of events led to the identification of MTHFR.

The point where it all started was in 1964 when the journal Science published a study with important discovery

You see, a team of scientists identified cystathionine beta-synthase (CBS) deficiency in mentally ill patients.

To clarify, the CBS gene provides instructions for making an enzyme of the same name. 

This enzyme works in a chemical pathway, and its responsibility is to use vitamin B6 and convert homocysteine and serine to cystathionine molecule.

The patients from the above-mentioned study experienced symptoms such as lower IQ, skeletal abnormalities, and dislocation of the optic lens. 

Later, this condition became known as homocystinuria.

The term homocystinuria refers to a group of metabolic disorders indicated by a buildup of homocysteine and elevated exertion of this amino acid in urine.

As the research into homocystinuria develops, the condition will be associated later with mutations of different genes, including MTHFR, but we’re not there yet.

Almost a decade later, in 1972, scientists discovered that patients suffering from homocystinuria also exhibited a decrease in methylenetetrahydrofolate reductase activity.

More Concrete Origins of MTHFR

What I mentioned above, where the first steps into the MTHFR discovery as scientists found symptoms in patients with homocystinuria were linked with decreased MTHFR activity.

More concrete findings on MTHFR were published in 1988 in the American Journal of Human Genetics.

This study found the same MTHFR decrease in lymphocytes among patients with cardiovascular disease. 

The research showed that there was no apparent clinical problem related to abnormal folate or homocysteine levels in patients with MTHFR deficiency in infancy and childhood.

However, vascular disorders occurred in adulthood. 

These observations suggest that deficiency in MTHFR could be associated with vascular disorders in adult life, scientists concluded.

Basically, this study found that MTHFR deficiency could jeopardize vascular health, and it marks the beginning of research on the impact of MTHFR on the risk of health problems.

The story continues…

For quite some time, the investigations into MTHFR deficiency were limited to the laboratories with expertise in biochemical genetics methodologies.

In 1994 the major breakthrough in this field happened; the cDNA was isolated.

Isolation of cDNA paved the way for molecular genetic approaches to study MTHFR deficiencies.

Just one year later, in 1995, the cDNA isolation was followed by the identification of a common sequence variant C677T. 

The research was first published in the journal Nature Genetics.

In a nutshell, scientists found that this particular variant of the MTHFR gene-altered highly-conserved amino acid (homocysteine).

Homozygous people (with two mutations of the MTHFR gene) had particularly elevated levels of homocysteine.

This gene variant has become recognized as the most prevalent genetic cause of hyperhomocysteinemia and has been investigated as a risk factor for several multifactorial disorders.

To this day, the greatest deal of research revolves around C677T.

But what about A1298C?

This gene variant was discovered back in 1998.

The journal Molecular Genetics and Metabolism featured a study that showed that homozygosity was observed in 10% of Canadian individuals.

This gene variant was linked with reduced enzyme activity, but scientists emphasized the need for further research.

Interestingly, this same study identified yet another gene variant (T1317C), but it was relatively infrequent.

Now it’s a good time to remind you that although C667T and A1298C are the most common MTHFR gene mutations, there are also other variants, and hopefully, studies will focus on them as well.

What is the future of MTHFR gene research?

MTHFR research has been a complex subject for decades…

As I’ve demonstrated above, many studies linked MTHFR mutations and the MTHFR enzyme with impaired homocysteine levels and vascular problems.

But, the research on this subject is far from over.

In 2021 there’s still we don’t know about MTHFR mutations, and hopefully, we’ll learn more about them in the near future.

At this point, little is known about the regulation of the MTHFR gene despite the fact it’s involved in the metabolism of folate and homocysteine, or DNA methylation, and other processes.

Regulatory regions and their modulations, in association with MTHFR gene mutations, require further studies.

The future of MTHFR gene research lies in investigations that shed light on all mechanisms of action associated with MTHFR mutations, their regulations, and their potential impact on other aspects of our health.

Insufficient exploration of MTHFR gene mutation doesn’t allow us to get a deep insight into this common occurrence and potential treatments to prevent or overcome problems associated with these variants.

When Was MTHFR Gene Discovered

When Was MTHFR Gene First Discovered? … It’s A Short, Complicated History But Being So Young We Hope To Learn More In The Coming Years.


The history of MTHFR (both enzyme and gene) is complicated. 

The story of MTHFR started long before the mutations were discovered, and their impact on vascular disease risk was outlined.

For many years scientists were explaining certain health problems that later turned out to be involved with MTHFR mutation, as seen above.

The whole MTHFR gene mutation subject is still young, and it’s safe to say we’re going to hear about it a lot in the coming years.

In this post, I aimed to show you when was MTHFR gene first discovered, and as you could see in 1994, cDNA was identified and C677T in 1995, which is why these years pose as the foundation for further research.