rs1801133(A;A)

This is the homozygous form of the C677T allele for the MTHFR gene. It is found in approximately * 15% of Hispanic Americans * 12% of Caucasian Americans * 12% of Japanese * 6% of Germans * 3% of Asians * 2% of African Americans * 1% of Sub-Saharan Africans Numerous health effects are associated with this variant. * Hyperhomocysteinemia and neurologic disorders: a review. (2014). A review. Certain genetic factors also cause elevated homocysteine levels, such as C667T substitution of the gene encoding methylenetetrahydrofolate reductase. Elevated homocysteine has been observed in several medical conditions, such as cardiovascular disorders, atherosclerosis, myocardial infarction, stroke, minimal cognitive impairment, dementia, Parkinson's disease, multiple sclerosis, epilepsy, and eclampsia. There is evidence from laboratory and clinical studies that homocysteine, and especially elevated homocysteine, exerts direct toxic effects on both the vascular and nervous systems. * Common folate gene variant, MTHFR C677T, is associated with brain structure in two independent cohorts of people with mild cognitive impairment. (2012): A commonly carried C677T polymorphism in a folate-related gene, MTHFR, is associated with higher plasma homocysteine, a well-known mediator of neuronal damage and brain atrophy.. … Carriers of the MTHFR risk allele had detectable brain volume deficits, in the white matter, of up to 2–8% per risk T allele locally at baseline and showed accelerated brain atrophy of 0.5–1.5% per T allele at 1 year follow-up. sciencedirect.com * Biological and clinical implications of the MTHFR C677T polymorphism. (2001). Under conditions of impaired folate status, the homozygous TT genotype has been regarded as harmful because it is associated with a high concentration of plasma total homocysteine. * One-Carbon Metabolism and Alzheimer’s Disease: Focus on Epigenetics. (2010). ncbi.nlm.nih.gov A review - numerous studies have shown that the MTHFR 677T allele is associated with increased total plasma homocysteine levels (tHcy) and decreased serum folate levels, mainly in 677TT homozygous subjects. Other studies have shown an interaction with the APOE4 variant in Alzheimer's disease. The C677T genotype is seen more frequently in mothers of children with Down syndrome, mothers also show more chromosomal damage than controls. * Association of RFC1 A80G and MTHFR C677T polymorphisms with Alzheimer's disease. (2009). Significant associations of T allele and TT genotype with Alzheimer's disease were identified in the APOE epsilon4 carrier subgroup, suggesting that MTHFR 677 T allele and APOE epsilon4 allele may synergistically act to increase AD risk. * Morton's foot and pyridoxal 5'-phosphate deficiency: Genetically linked traits. (2014). Supplementation with PLP, L5-MTHF, B12 and trimethylglycine should be used in those patients with hyperhomocysteinemia and/or MTHFR gene mutation.