Methylenetetrahydrofolate reductase polymorphisms in preeclampsia and the HELLP syndrome.
OBJECTIVE
To investigate the prevalence of the 677 (C --> T) and 1298 (A --> C) polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene in our preeclamptic population. For a summary estimation of the risk of the 677 (C --> T) polymorphism for preeclampsia, we also performed a meta-analysis on four previously published case-control studies to which our results were added.


METHODS
Genotypes were analyzed by polymerase chain reaction followed by restriction enzyme analysis. The results of 176 nonpregnant women, previously hospitalized for preeclampsia in a tertiary care center, were compared with 403 Dutch population-based controls. Results were statistically analyzed with a chi-square test.


METHODS
The incidence of the 677 (C --> T) and 1298 (A --> C) polymorphisms in the MTHFR gene.


RESULTS
The incidence of both MTHFR missense polymorphisms was not significantly different between cases and controls. We found an odds ratio (OR) of 1.5 [95% confidence interval (CI) 0.8-2.6, p = 0.17] and an OR of 1.0 (95% CI 0.6-1.9, p = 0.23) for the 677 (C --> T) and the 1298 (A --> C) polymorphism, respectively, in cases comparing the prevalence of the homozygous genotype versus the other two genotypes. The meta-analysis resulted in a significant OR of 2.0 (95% CI 1.4-2.9).


CONCLUSIONS
In contrast to four previous studies, we were neither able to confirm an increased risk for preeclampsia to the 677 (C --> T) polymorphism nor did we find an increased risk for preeclampsia to the 1298 (A --> C) polymorphism. From the meta-analysis, however, we conclude that it cannot be ruled out that the homozygous 677TT genotype is a modest but significant risk factor for preeclampsia.
Zusterzeel
P L
PL
Departments of Obstetrics and Gynaecology, University Hospital Nijmegen, Nijmegen, The Netherlands.
Visser
W
W
Blom
H J
HJ
Peters
W H
WH
Heil
S G
SG
Steegers
E A
EA
D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D005838:Genotype; D017359:HELLP Syndrome / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D015994:Incidence; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D020125:Mutation, Missense / Q000235:genetics; D009426:Netherlands / Q000453:epidemiology; D016017:Odds Ratio; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D011225:Pre-Eclampsia / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics*; D011247:Pregnancy; D015995:Prevalence; D012307:Risk Factors
D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)