The methylenetetrahydrofolate reductase 677 C-->T polymorphism and preeclampsia in two populations.
OBJECTIVE
The C677T polymorphism of the 5,10 methylenetetrahydrofolate reductase (MTHFR) gene is associated with decreased MTHFR activity and elevated plasma homocysteine levels with the result of an increased risk for vascular disease. Because thrombosis of the maternal spiral arteries can be one of the causative events in the disease, it has been suggested that the C677T polymorphism may also play a role in the pathogenesis of preeclampsia. Our case-control study investigated the prevalence of the 677T allele in two ethnically different populations and the potential association of the 677T allele with preeclampsia. Special attention was paid to the potential contribution of the fetal genotype to disease risk.


METHODS
Blood samples were collected from 81 mothers and 61 newborns after preeclampsia and 99 mothers and 61 newborns with normal pregnancies. Genomic DNA was amplified by polymerase chain reaction with locus-specific primers, and presence of the polymorphism was determined by enzymatic digestion with HinfI and visualization on polyacrylamide gels.


RESULTS
Genotypes carrying the MTHFR 677T allele were significantly more frequent in German-Croatians than in Indonesians in both patients and controls (P =.0033 in controls). In contrast, the prevalence of genotypes with the 677T allele was not increased among patients with preeclampsia compared with controls in both ethnic groups (P >.5 in all groups). In Germans, the frequency of 677T homozygotes among controls even exceeded that observed in preeclamptic patients (677T/T genotype frequency 0.20 in controls and 0.07 in patients). We did not find an increased prevalence of paternally inherited 677T alleles in preeclamptic fetuses relative to controls or other signs of maternal-fetal transmission distortion.


CONCLUSIONS
In our study, the MTHFR C677T polymorphism was not associated with an increased risk for preeclampsia on the level of the maternal or fetal genotype. However, significant differences of the frequency of genotypes carrying the 677T allele between Middle-Europeans and Indonesians were identified.
Prasmusinto
D
D
Department of Obstetrics and Gynecology, University of Bonn, Bonn, Germany.
Skrablin
S
S
Hofstaetter
C
C
Fimmers
R
R
van der Ven
K
K
D000328:Adult; D019943:Amino Acid Substitution; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D017523:Croatia / Q000453:epidemiology; D005260:Female; D005312:Fetal Blood; D015971:Gene Expression Regulation, Enzymologic; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007214:Indonesia / Q000453:epidemiology; D007231:Infant, Newborn; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D011110:Polymorphism, Genetic; D011225:Pre-Eclampsia / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics*; D011247:Pregnancy; D015995:Prevalence; D044465:White People / Q000235:genetics*
D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)