[Epidemiological study on reduced folate carrier gene(RFC1 A80G) polymorphism and other risk factors of neural tube defects].
OBJECTIVE
To study the reduced folate carrier gene (RFC1) A80G polymorphism and other factors influence on children with neural tube defects (NTDs) and provide the epidemiological evidence for finding genetic marker of NTDs.


METHODS
RFC1(A80G) genotypes were detected using polymerase chain reaction-restriction fragment length polymorphism (RFLP-PCR) for blood DNA of 104 trios with NTDs-affected by child, and the 100 control families without child-affected by any birth defects. We performed the analysis of multifactors logistic regression for RFC1 genotypes and other factors in order to investigate the RFC1 genotype of the nuclear families and maternal periconceptional folic acid supplementation influence on NTDs independently. Transmission/disequilibrium test (TDT) for the RFC1 genotype of NTDs and control pedigree were carried out.


RESULTS
The RFC1 G allele frequency of children with NTDs (64.42%) was higher than that of the control children (52.53%), and there was the significant difference between them (chi(2)=5.9198, P<0.05). We observed that the infants of the GG genotype were associated with a 2.56-fold increased risk of NTDs when compared with the AA genotype (95% CI=1.04-6.36), The risk of mothers who did not take folic acid for having an NTDs-affected infants was 7.69 (95% CI=2.86-21.75). There were significant differences between cases and controls in the other risk factors, such as paternal age (> or =30), maternal fever during the early pregnancy, the history of maternal spontaneous abortion. In the logistic regression analysis, of multifactors the three factors, for example, the offspring of the RFC1 GG genotype (OR=2.91, 95% CI=1.35-6.30), maternal periconceptional folic acid supplementation (OR=4.32, 95% CI=1.62-11.55), maternal fever during the early pregnancy, had the statistic significance for the risk of NTDs. There was the evidence of an association between G allele and the risk of the maternal having a child with NTDs (OR=1.56, 95% CI=1.07-2.28) in TDT analysis.


CONCLUSIONS
Our findings indicate that the RFC1 genotype (GG) is a possible susceptible gene marker for an increased NTDs risk in this Chinese population, and there is a potential influence on the risk of NTDs in maternal periconceptional folic acid supplementation, and maternal fever during the early pregnancy.
Pei
Li-jun
LJ
Institute of Reproductive and Child Health, National Reference Laboratory on Reproductive Health Research, Ministry of Health, Peking University, Beijing 100083, China.
Li
Zhi-wen
ZW
Zhang
Wei
W
Ren
Ai-guo
AG
Zhu
Hui-ping
HP
Hao
Ling
L
Zhu
Jiang-hui
JH
Li
Zhu
Z
D000328:Adult; D002648:Child; D002675:Child, Preschool; D002681:China / Q000453:epidemiology; D005192:Family Health; D005260:Female; D005494:Folic Acid Deficiency; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D007223:Infant; D016015:Logistic Models; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D009436:Neural Tube Defects / Q000453:epidemiology / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D058978:Reduced Folate Carrier Protein; D012307:Risk Factors
D005819:Genetic Markers; D026901:Membrane Transport Proteins; D058978:Reduced Folate Carrier Protein; C548699:SLC19A1 protein, human