Associations between maternal methylenetetrahydrofolate reductase polymorphisms and adverse outcomes of pregnancy: the Hordaland Homocysteine Study.
OBJECTIVE
Methylenetetrahydrofolate reductase (MTHFR) is involved in the metabolism of folate and homocysteine; a polymorphism in the MTHFR gene (677C-->T) has been associated with adverse outcomes of pregnancy. We studied whether two polymorphisms in the MTHFR gene (677C-->T and 1298A-->C) are associated with pregnancy complications, adverse outcomes, and birth defects.


METHODS
MTHFR polymorphisms were determined in blood collected in 1992 and 1993 from 5883 women aged 40 to 42 years, and linked with 14,492 pregnancies in the same women recorded in the Medical Birth Registry of Norway from 1967 to 1996.


RESULTS
The 677TT genotype in mothers was associated with increased risk of placental abruption (odds ratio [OR] = 2.6; 95% confidence interval [CI]: 1.4 to 4.8) compared with the CC variant. The risk of intrauterine growth restriction increased with number of T alleles (P for trend = 0.04). Compared with the 1298AA variant, the CC variant was associated with a reduced risk of very low birth weight infants (OR = 0.4; 95% CI: 0.2 to 0.8). No significant associations were found between MTHFR polymorphisms and birth defects.


CONCLUSIONS
The maternal MTHFR 677C-->T polymorphism was a risk factor for placental abruption. The unexpected protective effect of the 1298A-->C polymorphism on very low birth weight needs further study.
Nurk
Eha
E
LOCUS for Homosysteine and Related Vitamins, Department of Public Health and Primary Health Care, University of Bergen, Norway.
Tell
Grethe S
GS
Refsum
Helga
H
Ueland
Per M
PM
Vollset
Stein E
SE
D000037:Abruptio Placentae / Q000453:epidemiology / Q000235:genetics; D000328:Adult; D000483:Alleles; D000013:Congenital Abnormalities / Q000453:epidemiology / Q000235:genetics; D005260:Female; D005317:Fetal Growth Retardation / Q000453:epidemiology / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006579:Heterozygote; D006710:Homocysteine / Q000097:blood; D006801:Humans; D016015:Logistic Models; D008423:Maternal Age; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000453:epidemiology*; D011256:Pregnancy Outcome; D018566:Pregnancy, High-Risk; D012307:Risk Factors
D006710:Homocysteine; D042965:Methylenetetrahydrofolate Reductase (NADPH2)