A Case-control Study Of The Association Between MTHFR Gene Mutation And Neural Tube Defects

Objective: A case-control study was conducted in order to find out risk factors of neural tube defects (NTDs) , the relationship between mother Methylenetetrahydrofolatereductase (MTHFR) genotype and the risk of fetal neural tube defects (NTDS) was explored in shanxi province where the incidence rate of NTDS is the topest of China , Meanwhile , the study analysized the interactions between these risk factors . This could help to find out the causes of the disease and provide scientific evidence for health policies controlling this disease.Methods: It was designed as 1:1 matched case -control study, we choose 41 parturiens who had given birth to NTDS children as case group and 41 parturiens given birth to normal children as control group from counties higher accidence in NTDs in shanxi. All of the objects were investigated in uniform questionnaires about suspected risk factors for NTDS and were genotyped for MTHFR C677T and A1298C polymorphism by using PCR/RFLP method. All of the data was analysized with SPSS 10.0 and SAS 8.0 statistical software.Results: ( 1 ) Analysis of multiple variables logistic regression showed that mother MTHFR 677 mutation was one of the genetic risk factors of offspring NTDS . Fresh vegetableand fruit was enviromental protective factor, while germinated potato was environmental risk factor for fetal NTDS.C 2 ) Analysis of the relationship between MTHFR and NTDS show that :As far C677T, TT genotype frequency in the normal mothers group was 17.1%,while in the NTDs mothers was 34.1%, which was significantly different at 0.10 level( x 2 = 5.91, P=0.052, OR=2.64 ) . The frequency of alley T was significantly higher in case group at 61.0% than in normal control at 42.7% ( x2 = 2.75, P<0.10) . Furthermore, the elevated NTDS risk associated with the 677 polymorphism was in an allele-dose relationship (trend test x 2 = 9.84, P><0.005) with ORs of 1.00, 2.72 and 5.20 for CC, CT and TT genotype, respectively. Contrase to other regions and contries where NTDS incidence rate were low, the distribution of genotype of T/T was higher in shanxi privince. As far A1298C, having no the CC homozygosity ,heterozygosity AC genotype was not more prevalent in the neonatal group at 29.3% than in the normal control group at 24.4% ( x 2 = 0.25 , P>0.10) .the difference of attribution of alley C in two groups also did not show statistical significance (x2=0.21, P>0.10) .(3) Analysis of Interaction between factors showed that: combination of MTHFR C677T and A1298C polymorphisms on the risk of NTDs revealed there was no evidence of interaction between the two polymorphisms, but as the number of mutated alley adds, the OR increases accordingly .There was negative interaction between the polymorphism of MTHFR C677T and fresh vegetable ( Attributable Proportions OfInteraction:API =-0.42 ; the Synrtgy Index S= 0.41), freshvegetable could decrease the risk of fetal NTDS . Probably there was no interaction between the polymorphism of MTHFR C677T and germinated potato (Attributable Proportions Of Interaction: API = 0.02; the Synrtgy Index S=4.02) .Conclusion: Mother MTHFR 677 mutation was one of the genetic risk factors of offspring NTDS and high distribution of TT was probably one of reasons of its top NTDS incidence rate in shanxi. Fresh vegetable and fruit was enviromental protective factor ,which could decrease the risk of fetal NTDs . while germinated potato was environmental risk factor which was also considered probably one of reasons of top NTDS incidence rate in shanxi.