Mutations in the gene for methylenetetrahydrofolate reductase, homocysteine levels, and vitamin status in women with a history of preeclampsia.
OBJECTIVE
This study was undertaken to assess frequencies of the methylenetetrahydrofolate reductase gene mutations cytosine-to-thymine substitution at base 677 (C677T) and adenine-to-cytosine substitution at base 1298 (A1298C) and their interactions with homocysteine and vitamin levels among Dutch women with preeclampsia.


METHODS
Mutations were studied in the following 5 groups: 47 consecutive women with preeclampsia, 49 women with preeclampsia and with hyperhomocysteinemia, 36 women with preeclampsia but without hyperhomocysteinemia, 127 women with familial preeclampsia (typed for C677T mutations only), and 120 control subjects. Plasma levels of homocysteine, folate, and vitamin B12 were measured.


RESULTS
Although 10.6% of the consecutive women with preeclampsia had strictly defined hyperhomocysteinemia (values >97.5th percentile), neither mutation was found in excess relative to the control group. Women with preeclampsia who had mild hyperhomocysteinemia (values >75th percentile) had a significant excess of the TT genotype (homozygosity for C677T mutation) relative to the women with preeclampsia who did not have hyperhomocysteinemia (odds ratio, 8.2; 95% confidence interval, 1.8-39). They also had significantly lower vitamin levels.


CONCLUSIONS
Hyperhomocysteinemia in women with preeclampsia was associated with mutations in the gene for methylenetetrahydrofolate reductase, but the high frequency of hyperhomocysteinemia itself cannot be explained by these mutations alone.
Department of Clinical Genetics and Human Genetics, University Hospital Vrije Amsterdam, The Netherlands.
A M
AM
Lachmeijer
R
R
Arngrímsson
E J
EJ
Bastiaans
G
G
Pals
L P
LP
ten Kate
J I
JI
de Vries
P J
PJ
Kostense
J G
JG
Aarnoudse
G A
GA
Dekker
D001724:Birth Weight; D004247:DNA / Q000737:chemistry / Q000302:isolation & purification; D017931:DNA Primers / Q000737:chemistry; D015252:Deoxyribonucleases, Type II Site-Specific / Q000737:chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005492:Folic Acid / Q000097:blood; D005838:Genotype; D005865:Gestational Age; D017359:HELLP Syndrome / Q000097:blood / Q000201:enzymology / Q000235:genetics; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007231:Infant, Newborn; D016014:Linear Models; D008715:Methionine / Q000008:administration & dosage; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D009154:Mutation; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000097:blood / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011225:Pre-Eclampsia / Q000097:blood / Q000201:enzymology / Q000235:genetics*; D011247:Pregnancy; D011863:Radioimmunoassay; D012044:Regression Analysis; D014805:Vitamin B 12 / Q000097:blood*
D017931:DNA Primers; D006710:Homocysteine; D004247:DNA; D005492:Folic Acid; D008715:Methionine; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D015252:Deoxyribonucleases, Type II Site-Specific; C032229:GANTC-specific type II deoxyribonucleases; D014805:Vitamin B 12