B-vitamins, homocysteine and gene polymorphism in adults with fasting or post-methionine loading hyperhomocysteinemia

Abstract

Although fasting and post-methionine loading (PML) homocysteine concentrations are not necessarily related, a high percentage of hyperhomocysteinemia cases would be missed if methionine loading was not performed. The influences of B-vitamins and genetic polymorphism (methylenetetrahydrofolate reductase 677C --> T, MTHFR 677C --> T) on fasting and PML homocysteine concentrations and the relationship between fasting and PML homocysteine were studied. This study was a cross-sectional study. Healthy subjects were divided into either fasting hyper-homocysteinemia (>or=12.2 micromol/l) (fasting hyper-hcy, n = 51), PML hyper-homocysteinemia (fasting homocysteine <12.2 micromol/l but PML homocysteine >or=25.6 micromol/l) (PML hyper-hcy, n = 29), or normo-homocysteinemia (fasting homocysteine <12.2 micromol/l and PML homocysteine <25.6 micromol/l) (normo-hcy, n = 118) group based on elevated fasting and PML homocysteine levels of the 75th percentile of the population. The concentrations of plasma fasting and PML homocysteine, serum folate, vitamin B-12, plasma pyridoxal 5'- phosphate (PLP) were measured. The genetic polymorphisms were determined. Fasting homocysteine, but not PML homocysteine and MTHFR 677C --> T genotype, was significantly and inversely affected by serum folate concentration after adjusting for potential confounders (beta = -0.062, P < 0.01). Fasting and PML homocysteine were highly associated in the fasting hyper-hcy and pooled groups (P < 0.01) but not in the PML hyper-hcy and normo-hcy groups. PML homocysteine did not interact with either serum folate (P = 0.302), vitamin B-12 (P = 0.465), plasma PLP (P = 0.996) or MTHFR 677C --> T genotype (P = 0.136) to affect fasting homocysteine concentration. Approximately one-third (36.3%) of hyperhomocysteinemia cases would be missed if methionine loading were not performed. Even though subjects may have a normal fasting homocysteine concentration, they need further screening for their PML homocysteine.