677C-->T and 1298A-->C together = "haplotype"............
J Mol Med 2001 Sep;79(9):522-8
A second common variant in the methylenetetrahydrofolate reductase
(MTHFR) gene and its relationship to MTHFR enzyme activity,
homocysteine, and cardiovascular disease risk.
Lievers KJ, Boers GH, Verhoef P, den Heijer M, Kluijtmans LA, van Der Put NM,
Trijbels FJ, Blom HJ.
Department of Pediatrics, University Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The
Netherlands.
Molecular defects in genes encoding enzymes involved in homocysteine metabolism may account
for mild hyperhomocysteinemia, an independent and graded risk factor for cardiovascular disease
(CVD). We examined the relationship of two polymorphisms in the methylenetetrahydrofolate
reductase (MTHFR) gene, the 677C-->T and 1298A-->C variants, to MTHFR activity,
homocysteine concentrations, and risk of CVD in a population of 190 vascular disease patients
and 601 apparently healthy controls. The mean specific and residual MTHFR activities were
significantly lower in 677CT and 677TT individuals (both P<0.001). The 1298A-->C mutation
alone showed no effect on MTHFR activities. However, when the 677C-->T genotype was
taken into account, the 1298A-->C mutation also caused a significant decrease in MTHFR
activities, which was observed in both the homozygous 1298CC (P<0.001) and the
heterozygous 1298AC states (P=0.005). Both the 677TT as the 677CT genotypes were
associated with significantly higher fasting and postload homocysteine levels than 677CC
(P<0.001 and P=0.003, respectively). The 1298A-->C mutation had no effect on fasting or
postload homocysteine levels. Since homocysteine itself is considered to be positively associated
with the risk of CVD, these findings indicate that the 1298A-->C mutation cannot be considered
a major risk factor for CVD. |
