The Genetics of MTHFR

The most important thing to understand about genetics is that no one really understands it. The study of genetics and genetic disorders is so new, that it is like a giant jigsaw puzzle. Researchers have learned to identify the pieces, but they’ve just started putting them together.

The gene sequence which is involved in making MTHFR is one of the pieces that researchers have identified. More importantly, they have begun to recognize different forms of the gene. These different forms are called ‘polymorphisms’. So far, researchers have identified over 40 MTHFR polymorphisms, and nine of these MTHFR polymorphisms are common. So far, significant research has only been done on two.

The lack of research into most of the MTHFR polymorphisms isn’t because scientists and doctors aren’t doing all the research they can. It’s simply that there are not enough researchers to study all the MTHFR polymorphisms at the same time. So research has focused on the two most common ones. In time, researchers will learn about all of the MTHFR polymorphisms.

The two MTHFR polymorphisms that have been studied are called C677T and A1298T. C667T means that at the location 677 on the gene sequence, a gene that is supposed to be C (Cytosine) has been replaced with T (Thymine). A1298T means that a gene that was supposed to be A (Adenine) has been replaced with G (Guanine).

They are generally referred to as MTHFR 677 and MTHFR 1298. These are the two most common MTHFR polymorphisms. Around 40% of people with have either MTHFR 677, MTHFR 1298, or both.

The changes in the genetic code created by these polymorphisms change the enzyme, MTHFR. These changes affect how well MTHFR works and how it interacts with other chemicals in the body. Many health problems may be caused when MTHFR doesn’t work properly.Since each polymorphism changes MTHFR in a different way, each one creates a different variety of MTHFR, or MTHFR anomaly. This means each genetic polymorphism will lead to different health problems.

In addition to differences between polymorphisms, there is the wide variety of differences created by the combination of polymorphism and normal genes. Everyone has two copies of each gene, one from their mother and one from their father. This means that a person can two have normal copies of the gene, one copy with a polymorphism, two copies with the same polymorphism, or two copies with different polymorphisms.

When both genes are the same, doctors say they are ‘homozygous’. If the genes are different they are called ‘heterozygous’.

If you get genetic testing for MTHFR polymorphisms, the test results will come back saying one of the following:
• homozygous normal (both genes are normal)
• homozygous 677
• homozygous 1298
• heterozygous normal/677
• heterozygous normal/1298
• 677/1298

Each of these combinations have different effects on the body, and produce different problems and symptoms. 677/1298 is the version which creates the most problems