The purpose of this study was to evaluate whether the interactions between maternal folate deficiency and methylenetetrahydrofolate reductase (MTHFR) polymorphism increase the risk of elevated maternal serum homocysteine, short gestation and reduced infant birthweight. Healthy pregnant (n = 170; 24-...
The purpose of this study was to evaluate whether the interactions between maternal folate deficiency and methylenetetrahydrofolate reductase (MTHFR) polymorphism increase the risk of elevated maternal serum homocysteine, short gestation and reduced infant birthweight. Healthy pregnant (n = 170; 24-28 gestational weeks; 20-40 years old) women were analyzed for the MTHFR genotype and serum levels of folate and homocysteine, and were then followed for gestational age and infant birthweight. The mean infant birthweight was highest in mothers carrying MTHFR CC and with a normal folate range, and they were followed by mothers carrying MTHFR CT or TT and a normal range of folate or a folate deficiency. Birthweight was the lowest in mothers whose carrying MTHFR CC with folate deficiency. Using two way ANOVA, we found that folate level and the MTHFR polymorphism interacted to affect birth-weight of infants (p=0.05). Among those mothers carrying MTHFR CC, those with folate deficiency showed a 543 g reduction in infant birthweight compared with those with normal folate levels. However, infant birthweight was no different for mothers, those who with folate deficiency compared to those with normal range of folate among mothers carrying the MTHFR CT or TT genotypes. This study suggests an interaction between maternal serum folate and the MTHFR polymorphisms of the mother on the risk of delivering reduced birthweight offspring. Folate supplementation of folate deficient pregnant women with the MTHFR wild type is suggested to reduce the risk of low birthweight.
The purpose of this study was to evaluate whether the interactions between maternal folate deficiency and methylenetetrahydrofolate reductase (MTHFR) polymorphism increase the risk of elevated maternal serum homocysteine, short gestation and reduced infant birthweight. Healthy pregnant (n = 170; 24-28 gestational weeks; 20-40 years old) women were analyzed for the MTHFR genotype and serum levels of folate and homocysteine, and were then followed for gestational age and infant birthweight. The mean infant birthweight was highest in mothers carrying MTHFR CC and with a normal folate range, and they were followed by mothers carrying MTHFR CT or TT and a normal range of folate or a folate deficiency. Birthweight was the lowest in mothers whose carrying MTHFR CC with folate deficiency. Using two way ANOVA, we found that folate level and the MTHFR polymorphism interacted to affect birth-weight of infants (p=0.05). Among those mothers carrying MTHFR CC, those with folate deficiency showed a 543 g reduction in infant birthweight compared with those with normal folate levels. However, infant birthweight was no different for mothers, those who with folate deficiency compared to those with normal range of folate among mothers carrying the MTHFR CT or TT genotypes. This study suggests an interaction between maternal serum folate and the MTHFR polymorphisms of the mother on the risk of delivering reduced birthweight offspring. Folate supplementation of folate deficient pregnant women with the MTHFR wild type is suggested to reduce the risk of low birthweight.
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문제 정의
However, the possible effect of an interaction between maternal folate and the MTHFR polymorphism on infant birthweight has not been investigated. The purpose of this study is to evaluate whether an interaction between maternal folate deficiency and the MTHFR CT and TT variants increases the risk of a reduced infant birthweight.
가설 설정
In this study, we found that folate deficiency alone is not associated with the risk of an increased serum level of homocysteine. However, the MTHFR variant was significantly associated with increased homocysteine levels in the presence of folate deficiency.
제안 방법
Finally, we estimated the risk of folate deficiency versus normal folate levels, on serum homocysteine, gestational age, and infant birthweight by using a linear regression model. We also adjusted for age, prepregnancy BMI, weight gain, height, and smoke exposure status.
This study has some limitations that we could not obtained information about infant MTHFR polymorphism, could not consider the potential relevance of fetal genotype, and could not obtained information about prenatal vitamins or folic acid supplementation after folate measurement to delivery. However, prenatal vitamins or folic acid is not routine recommendation for pregnancy in South Korea.
Serum homocysteine levels, gestational age, and infant birthweight by MTHFR genotype and serum folate were compared by ANOVA and the student t- test. To determine the risk of folate and 사le MTHFR genotype on serum homocysteine, gestational age, and infant birthweight, we placed those with less than 3.0 ng/ml of folate in the folate deficiency group16 and those with MTHFR 677CT or 677TT in the MTHFR variant group. Two-way ANOVA testing was used to determine the interaction between folate and MTHFR.
대상 데이터
The study protocol was approved by the Institutional Review Board on human subjects at Ewha Womans University, Seoul, Korea, and informed consent was obtained from participants. The study subjects were 170 healthy pregnant women who visited an obstetric clinic for antenatal care and their singleton li\e births in Seoul, Korea between August 2001 and March 2003. The criteria for a healthy pregnant woman were as follows: no previous pregnancy complication, no medication, and free of chronic disease (pregnancy induced hypertension, gestational diabetes, and so on).
데이터처리
*MTHFR, methylenetetrahydrofolate reductase; FN, normal range of folate; FD, folate deficiency; CC, 677CC; CT, 677CT; TT, 677TT, fDetermined by two-way ANOVA test, p = 0.09 for folate group, p = 0. 98 for MTHFR types, and p = 0.
Serum homocysteine levels, gestational age, and infant birthweight by MTHFR genotype and serum folate were compared by ANOVA and the student t- test. To determine the risk of folate and 사le MTHFR genotype on serum homocysteine, gestational age, and infant birthweight, we placed those with less than 3.
0 ng/ml of folate in the folate deficiency group16 and those with MTHFR 677CT or 677TT in the MTHFR variant group. Two-way ANOVA testing was used to determine the interaction between folate and MTHFR.
이론/모형
The relations between folate deficiency and homocysteine level, gestational age, or infant birthweight considering MTHFR variants, interaction term of folate deficiency and MTHFR variants, prepregnancy BMI, weight gain, height, and smoke exposure status for all subjects were figured using GAM models in SPLUS version 11.0. Gestational age was additionally adjusted for only to the infant birthweight model.
성능/효과
This finding does not mean that MTHFR variant genotypes are unrelated to birthweight. As shown in this study, infant birthweights in pregnant women with the MTHFR variant genotypes were low compared to those with the MTHFR wild type. This result suggests that the MTHFR variant genotype itself or MTHFR variant gene-related factors, other than folate, influence infant birthweight.
In conclusion, the present study suggests a geneenvironment interaction between maternal serum folate during pregnancy and the MTHFR polymorphisms of the mother on the risk of delivering low birthweight offspring. Folate supplementation during pregnancy in the MTHFR wild type woman with folate deficiency is considered to reduce the likelihood of low birthweight.
This difference was more apparent when subject were further classified in terms of MTHFR polymorphisms. The magnitude of homocysteine level, gestational age and infant birthweight changes between those deficient in folate and those with normal folate levels were significantly greater for those with MTHFR 677CC. On the other hand, the homocysteine levels, gestational ages and infant birthweights were not different between folate deficient and normal folate groups among the MTHFR CT or TT types.
rnol/1). The percentages of the individual MTHFR genotypes were 34.1% for the 677CC homozygote, 48.8% for the 677CT heterozygote, and 17.1% for the 677TT homozygote. The average gestational age was 38.
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