The rs1801133 variation is a specific genetic alteration within the MTHFR gene. This common marker, often found through genetic testing, represents a subtle difference in the genetic code. It can influence how the body processes folate, a B vitamin.
The MTHFR Gene and Its Function
The MTHFR gene provides instructions for creating an enzyme called methylenetetrahydrofolate reductase. This enzyme functions in a biochemical pathway known as the folate cycle. Its primary role is to convert 5,10-methylenetetrahydrofolate into 5-methyltetrahydrofolate, which is the active form of folate the body can readily use.
This active form of folate is significant for a process called methylation, which involves adding methyl groups to various molecules. Methylation supports DNA synthesis and repair, and the regulation of gene expression. The MTHFR enzyme’s action is also involved in converting the amino acid homocysteine into another amino acid, methionine. This conversion is important for maintaining appropriate homocysteine levels in the body.
Understanding the rs1801133 Variation
The rs1801133 variation is also known as C677T. This designation indicates a specific change at position 677 in the MTHFR gene’s DNA sequence. Normally, at this position, the DNA letter is cytosine (C), but in the variant form, it is thymine (T).
Individuals inherit two copies of each gene, one from each parent. Three possible combinations, or genotypes, can exist for the C677T variation: C/C, C/T, and T/T. A C/C genotype means both copies have the typical ‘C’ allele, resulting in normal enzyme function. A C/T genotype means one copy has the ‘C’ allele and the other has the ‘T’ allele, indicating a heterozygous state. Individuals with a C/T genotype typically experience a reduction in MTHFR enzyme activity by about 30-40%.
The T/T genotype means both copies carry the ‘T’ allele, representing a homozygous variant. Individuals with this genotype have a more pronounced reduction in enzyme activity, typically ranging from 60-70% compared to those with the C/C genotype. This alteration results in a less stable MTHFR enzyme that functions with reduced efficiency.
Associated Health Conditions
Reduced MTHFR enzyme function resulting from the rs1801133 variation can lead to an elevation of homocysteine levels in the blood, a condition referred to as hyperhomocysteinemia. High homocysteine levels are considered a risk factor for various health concerns.
There is an association between the rs1801133 variation and an increased risk of neural tube defects in offspring when the mother carries the variation, particularly if folate levels are low. These are serious birth defects, such as spina bifida. The variation has also been associated with cardiovascular issues, including an increased risk of stroke and blood clots. Elevated homocysteine may contribute to these risks by affecting vascular health.
The rs1801133 variation has been linked to certain pregnancy complications, such as recurrent miscarriage and pre-eclampsia. Having the rs1801133 variation does not guarantee the development of these conditions. Many factors influence health outcomes, and genetic variations are one piece of a complex puzzle.
Management and Nutritional Considerations
For individuals with the rs1801133 variation, particularly those with the T/T or C/T genotypes, nutritional considerations involve distinctions in folate intake. Synthetic folic acid, commonly found in fortified foods and many standard supplements, needs to be converted by the body into its active form to be utilized. Individuals with reduced MTHFR enzyme activity may have difficulty efficiently performing this conversion.
Consuming folate from natural food sources, such as dark leafy greens, legumes, and liver, can be beneficial. These foods naturally contain folate in forms that are more readily used by the body. Alternatively, supplements containing L-methylfolate (also known as 5-MTHF) can be considered, as this is the active form of folate that bypasses the conversion step requiring the MTHFR enzyme.
Other B vitamins, such as B6 (pyridoxal phosphate) and B12 (cobalamin), also play supportive roles in the methylation cycle and homocysteine metabolism. Supplementation with these vitamins, along with folate, has been shown to normalize homocysteine levels in some cases. Any changes to diet or the initiation of new supplement regimens should only occur after consultation with a qualified healthcare provider for personalized guidance.