What you carry at this position in your DNA and what research says about it.
Folate and Drug Metabolism: 5/10 evidence, 56 publications.
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Sample genotype (not yours): A/A
Typical Folate Metabolism and Standard Drug Response
This genotype is associated with typical methionine synthase activity and standard processing of folate. It generally indicates a lower risk of toxicity from certain chemotherapy drugs and a typical response to blood pressure medications.
What this genotype means: Typical folate metabolism; Standard response to benazepril; Lower risk of methotrexate toxicity.
Sample genotype (not yours): A/G
Altered Folate Processing and Variable Drug Response
Carrying one copy of the G allele may slightly alter folate metabolism and reduce the effectiveness of certain blood pressure medications. It is also linked to a better response to some combination therapies.
What this genotype means: Slightly altered folate metabolism; Reduced response to benazepril; Potential for better response to certain combination therapies.
Sample genotype (not yours): G/G
Increased Risk of Drug Toxicity and Reduced Drug Response
Carrying two copies of the G allele is linked to slower metabolism of certain medications, increasing the risk of drug toxicity. It may also reduce the effectiveness of some blood pressure treatments.
What this genotype means: Increased risk of methotrexate toxicity; Poorer response to benazepril; Higher risk of chemotherapy-induced side effects.
Gene function and biological role
Gene Function: The MTR gene encodes methionine synthase, a key enzyme that links folate metabolism with the body's methylation cycle. This enzyme is responsible for converting homocysteine to methionine, a building block for proteins and vital cellular compounds. Proper functioning of this pathway is essential for maintaining healthy DNA methylation and preventing the buildup of homocysteine. Variations in this gene can influence how efficiently the body processes folate and responds to certain medications.
Variant Impact: The rs1805087 variant, also known as A2756G or p.Asp919Gly, is a common missense mutation in the MTR gene that swaps the amino acid aspartate for glycine. This change occurs in the binding domain of the enzyme and can alter its overall activity. While some studies suggest the variant allele may affect enzyme efficiency and folate levels, clinical databases classify it as benign for causing severe congenital disorders on its own. However, it remains highly relevant for its influence on drug responses and metabolic efficiency.
Key Insight: This variant does not cause severe congenital disorders on its own, but it significantly influences how your body metabolizes common medications like methotrexate and blood pressure drugs.
Location: MTR. Chromosome 1 · 1q43 · 236.9 Mb
Estimated prevalence by population
Global 62.1%; European 64.7%; African 54.4%; East Asian 77.2%; South Asian 47.4%; Americas 66.6%; Ashkenazi 68.0%; Finnish 65.8%; Middle Eastern 70.0%; Amish 65.6%.
Estimated AA genotype frequency.
Global 33.2%; European 31.5%; African 38.7%; East Asian 21.3%; South Asian 42.9%; Americas 30.0%; Ashkenazi 28.9%; Finnish 30.6%; Middle Eastern 27.3%; Amish 30.8%.
Estimated AG genotype frequency.
Global 4.7%; European 3.8%; African 6.9%; East Asian 1.5%; South Asian 9.7%; Americas 3.4%; Ashkenazi 3.1%; Finnish 3.6%; Middle Eastern 2.7%; Amish 3.6%.
Estimated GG genotype frequency.
Showing effects for A/A genotype
Nutrition & Metabolism
Vitamin & Mineral Metabolism
Folate Metabolism. Evidence: 5/10. Source: PMID 18322994. Typical.
Pharmacogenomics
Immunosuppressant & Biologic Response
Methotrexate Toxicity. Evidence: 5/10. Source: PMID 38381003. Typical Risk.
Cardiovascular Drug Response
Benazepril Response. Evidence: 5/10. Source: PMID 15148588. Typical Response.
Chemotherapy Response
Chemotherapy Toxicity. Evidence: 5/10. Source: PMID 19159907. Typical Risk.
Showing effects for A/G genotype
Folate Metabolism. Evidence: 5/10. Source: PMID 18322994. Altered.
Benazepril Response. Evidence: 5/10. Source: PMID 15148588. Poorer Response.
Showing effects for G/G genotype
Methotrexate Toxicity. Evidence: 5/10. Source: PMID 38381003. Increased Risk.
Chemotherapy Toxicity. Evidence: 5/10. Source: PMID 19159907. Increased Risk.
What this genotype means for the people who carry it
Sample genotype: AA (Homozygous)
Carrying two copies of the common A allele represents the baseline genetic profile for methionine synthase activity. Individuals with this genotype typically maintain standard folate metabolism and do not have the elevated risks of drug toxicity associated with the variant G allele. Research indicates a standard response to the blood pressure medication benazepril, avoiding the reduced efficacy seen in variant carriers. Additionally, studies on rheumatoid arthritis treatments show a favorable response to combination therapies containing folic acid and sulfasalazine. While this genotype is protective against certain metabolic inefficiencies, maintaining adequate intake of B-vitamins remains important for overall cardiovascular and cellular health.
Typical folate metabolism; Standard response to benazepril; Lower risk of methotrexate toxicity.
Sample genotype: AG (Heterozygous)
This heterozygous genotype represents a middle ground in methionine synthase activity, carrying one standard and one variant allele. Individuals with this profile may experience subtle differences in how their bodies process folate and manage homocysteine levels. Clinical studies have observed a poorer blood pressure response to the medication benazepril compared to those with the typical genotype. On the other hand, some research suggests that carriers of this variant may show a better response to certain combination therapies used for rheumatoid arthritis. While the single copy of the G allele is generally benign and does not cause severe health conditions, it suggests a need to monitor B-vitamin status to support optimal methylation.
Slightly altered folate metabolism; Reduced response to benazepril; Potential for better response to certain combination therapies.
Sample genotype: GG (Homozygous)
Having two copies of the variant G allele significantly impacts how the body processes several common medications. Pharmacogenomic studies show that this genotype is associated with slower metabolism of methotrexate, leading to a higher likelihood of drug toxicity and the development of rheumatoid nodules. There is also an increased risk of toxicity when undergoing chemotherapy with drugs like cisplatin, cyclophosphamide, or doxorubicin. Furthermore, individuals with this genotype may experience a poorer blood pressure response to benazepril. While this variant is considered benign for severe congenital disorders, it plays a critical role in determining how one tolerates and responds to specific medical therapies.
Increased risk of methotrexate toxicity; Poorer response to benazepril; Higher risk of chemotherapy-induced side effects.
Variants with shared genetic architecture
rs1532268 · MTRR Gene · Chr 5 · Folate and Methylation
rs1801133 · MTHFR Gene · Chr 1 · Folate Processing
rs1801131 · MTHFR Gene · Chr 1 · Folate Metabolism
Content updated August 2026.
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