Figure 1.
Simplified schematic of the folic acid metabolic cycle.
Folate receptors transport dietary folate into cells and the folate is converted into dihydrogolate (DHF) then tetrahydrofolate (THF) by dihydrofolate reductase (DHFR). In the folate metabolic cycle, THF is converted to 5,10-methyleneTHF, a substrate of 5,10-methyleneTHF reductase (MTHFR), then to 5-methylTHF. 5-methylTHF can be recycled by methionine synthase/methionine synthase reductase (MTR/MTRR) to THF and methionine. Alternatively, 5-methylTHF can be use to synthesize purine. The Methionine can be used in the methionine cycle to produce S-Adenosyl-methionine (SAM), S-adenosyl-homocysteine (SAH) and homocysteine. Conversion of SAM to SAH requires betaine, a product of choline metabolism. SAM is a major cellular methylation agent for DNA, RNA, protein, and phospholipids.
Table 1.
Ethnicities of individuals in the study.
Figure 2.
Genomic structure of the MTHFR gene and the location of the seven SNPs examined in this study.
Shaded boxes represent the exons (1 to 12) of MTHFR gene and the line in between represent intron regions. Distances and locations are approximate.
Table 2.
White and Hispanic MM individuals genotyped.
Table 3.
Allele frequency of seven SNPs in the MTHFR locus of White and Hispanic MM individuals in the study.
Table 4.
Case-Control Analyses of ADHD phenotypes in White subjects with MM.
Table 5.
Case-Control Analyses of ADHD phenotypes in Hispanic subjects with MM.
Table 6.
Linkage disequilibrium analysis of rs4846049 versus the other six SNPs tested.
Table 7.
Haplotype analyses of MTHFR SNPs and ADHD in White subjects with MM.