Non-fasting reference intervals for the Abbott IMx TM homocysteine and AxSYM TM plasma folate assays: influence of the methylenetetrahydrofolate reductase 677 C→T mutation on homocysteine

Plasma homocysteine comes under both genetic and nutritional control. B vitamins and particularly folate are important factors in homocysteine metabolism. We have obtained reference intervals for total plasma homocysteine and plasma folate. We have also determined the influence of methylenetetrahydrofolate reductase (MTHFR) genotype on plasma homocysteine concentrations in healthy individuals. Reference intervals for Abbott IMx homocysteine and AxSYM plasma folate assays were established using 116 volunteers recruited from hospital staff. Exclusion criteria included cardiac, hepatic or renal disorders, and use of over-the-counter prescription medications. An exception was the inclusion of three women using oral contraceptives and one woman receiving post-menopausal oestrogen supplementation. Methylenetetrahydrofolate reductase 677C-->T genotyping was performed on 101 of the volunteers to determine whether the MTHFR 677T allele influences homocysteine concentrations in healthy individuals. Reference intervals for homocysteine and folate were determined using the mean+/-2 standard deviations of the data. Folate/homocysteine ratios were sorted by MTHFR C677T genotype. Homocysteine correlated negatively with plasma folate. Mean male homocysteine concentrations were significantly higher (9.0 micromol/L; P<0.05) than the mean value (7.1 micromol/L) obtained for females. Mean homocysteine values were significantly higher in subjects who were homozygous for the MTHFR 677T allele when compared with the 677CC genotype (P<0.05). Ratios of folate/homocysteine were 20% and 7.4% lower in the male and female 677TT group than in the 677CC group, respectively. The mean homocysteine value of 43 volunteers who were taking multivitamins was not significantly different from that of 73 who were not vitamin supplemented. Conversely, the mean folate value was slightly greater, and statistically significant, in the group taking vitamin supplements. The mean folate values and reference intervals were not significantly different when grouped by sex or age. MTHFR 677C-->T mutations influenced homocysteine values observed in our study of healthy volunteers, even though we did not observe outright folate-deficient individuals. Our random homocysteine values were similar to the fasting homocysteine values obtained in other studies.