MTHFR (methylenetetrahydrofolate reductase) gene testing identifies common variants in the MTHFR gene, particularly C677T and A1298C. These variants reduce the efficiency of the MTHFR enzyme, which converts folate into its active form (5-methyltetrahydrofolate, or 5-MTHF) required for the methylation cycle, homocysteine remethylation, and DNA synthesis.

The C677T homozygous variant (two copies) reduces enzyme activity by 60-70% and is associated with elevated homocysteine (particularly when folate intake is low), increased neural tube defect risk in pregnancy, and possible cardiovascular risk. However, MTHFR variants are very common (about 10-15% of people carry two C677T copies) and their clinical significance in the absence of elevated homocysteine is debated. Testing provides guidance for folate supplementation strategy.