What is the Origin of MTHFR Variant?

The term is a concise clinical reference to a specific genetic alteration within the "MTHFR" gene, with "Variant" denoting the deviation from the most common gene sequence. Its relevance to hormonal health lies in the enzyme's role in the metabolic pathway that processes B vitamins necessary for estrogen metabolism and detoxification in the liver.

What is the Mechanism of MTHFR Variant?

The MTHFR enzyme catalyzes a crucial step in the folate cycle, which is directly linked to the methionine cycle, the primary source of S-adenosylmethionine (SAMe), the universal methyl donor. A variant with reduced enzyme activity results in less efficient production of 5-MTHF and, consequently, lower SAMe levels, impairing critical methylation reactions, including the Catechol-O-Methyltransferase (COMT) enzyme responsible for metabolizing catecholamines and estrogen. This impaired estrogen detoxification pathway can lead to a buildup of potentially undesirable estrogen metabolites, impacting the body's overall endocrine balance.

MTHFR Variant

Meaning

An MTHFR variant refers to a common single nucleotide polymorphism (SNP), or genetic mutation, in the methylenetetrahydrofolate reductase gene, most notably the C677T and A1298C polymorphisms. This genetic variation can lead to reduced functional efficiency of the MTHFR enzyme, which is essential for converting the inactive form of folate (5,10-methylenetetrahydrofolate) into the active form (5-methyltetrahydrofolate or 5-MTHF). The clinical implication of this reduced function is impaired methylation, a critical metabolic process affecting hormone detoxification, neurotransmitter synthesis, and DNA integrity.