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G Polymorphism Is Associated with Increased Plasma Homocysteine Concentration When Combined with the Homozygous Methylenetetrahydrofolate Reductase 677CT Variant1,2
Food Science and Human Nutrition Department and * General Clinical Research Center, University of Florida, Gainesville, FL 32611
3To whom correspondence should be addressed. E-mail: lbbailey{at}mail.ifas.ufl.edu.
Methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) are important for homocysteine remethylation. This study was designed to determine the influence of genetic variants (MTHFR 677C
T, MTHFR 1298AC, and MTRR 66AG), folate, and vitamin B-12 status on plasma homocysteine in women (20–30 y; n = 362). Plasma homocysteine was inversely (P < 0.0001) associated with serum folate and plasma vitamin B-12 regardless of genotype. Plasma homocysteine was higher (P < 0.05) for women with the MTHFR 677 TT/1298 AA genotype combination compared with the CC/AA, CC/AC, and CT/AA genotypes. Women with the MTHFR 677 TT/MTRR 66 AG genotype had higher (P < 0.05) plasma homocysteine than all other genotype combinations except the TT/AA and TT/GG genotypes. There were 5.4-, 4.3-, and 3.8-fold increases (P < 0.001) in risk for plasma homocysteine in the top 5, 10, and 20%, respectively, of the homocysteine distribution for subjects with the MTHFR 677 TT compared with the CC and CT genotypes. Predicted plasma homocysteine was inversely associated with serum folate (P = 0.003) and plasma vitamin B-12 (P = 0.002), with the degree of correlation dependent on MTHFR 677CT genotype. These data suggest that coexistence of the MTHFR 677 TT genotype with the MTRR 66AG polymorphism may exacerbate the effect of the MTHFR variant alone. The potential negative effect of combined polymorphisms of the MTHFR and MTRR genes on plasma homocysteine in at-risk population groups with low folate and/or vitamin B-12 status, such as women of reproductive potential, deserves further investigation.
KEY WORDS: • folate • genetic polymorphisms • homocysteine • vitamin B-12
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