| Objective: A case-control study was conducted in order to find out environmental risk factors of neural tube defects(NTDs).Meanwhile, it also intend to explore the relationship between mother Methionine synthase (MS)and 5, 10-Methylenetetrahydrofolate reductase (MTHFR)and offspring susceptibility to NTDs. The study analysized the interactions between these risks factor. This could help to find out the causes of NTDs and provide scientific evidence for health policies controlling NTDs.Methods: It was designed as l:lmatched case-control study, we choose 51 mothers who had given birth to at least one NTDs children as case group and 51 mothers given birth to normal children as control group They were all from counties in shanxi province, the incidence rate of which was the highest in China. All of the objects were investigated in uniform questionnaires about suspected risk factors for NTDs and were genotyped for MS A2756G and MTHFR C677T polymorphism by using PCR-RFLP method. All of the data was analysized with SPSS10.0 and SAS8.0 statistical software.Result: (1) Analysis of multiple variables logistic regression show that not mother MS A2756G, but MTHFR C677T mutation was one of the genetic risk factors of offspring NTDs. Eating fresh vegetable and fruit was environmental protective factor, while germinated potato was environmental risk factor for NTDs.(2) Analysis of the relationship between gene polymorphism and NTDs show that: as for MS A2756G, frequencies of A2756A,A2756G genotypeswere78.4% and 21.6% respectively in case group, 84.3% and 15.7% for control group (x2=0.58,P>0.10). Allele frequencies of A and G were0.892 and 0.108 in case group respectively, 0.922 and 0.078 in control group( x 2=0.52,#>0.10).As for MTHFR C677T, frequencies of CC,CT,TT were 19.6%,49.0%,31.4% in case group respectively,43.1%,43.1%,13.8% in control group respectively, which was significantly different at 0.001 level (x2=l7.90,P<0.001).Furthermore, with the increase of the number of mother allele T, the risk of offspring NTDs was elevated(trend test=8.06 P<0.01). Allele frequencies of C and T wereO.441, 0.559 in case group respectively, 0.647 and 0.353 in control group respectively ( x 2=18.85,P<0.001).(3)Comparison of MTHFR gene between population in Shanxi and other areas showed that: As for the genotype of MS gene, there were not significant difference in the frequency distribution between Hans in Shanxi and changsha HuNan population( x 2=0.6,P>0.05),while the difference between Hans in Shanxi and Japanese(x2=8.1,P <0.05)and California population (X=7A,P(0.05)were notable. Meanwhile, distribution of MTHFR genotype frequencies of Hans in Shanxi exist notable discrepancy with GuangDong population( x 2=13.1,P<0.01) and Hans in Beijing ( x 2=13.1,P<0.01) .In addition, Allele frequency among Hans in Shanxi is higher significantly than GuangDong population ( x 2=46.9,P<0.0\), Hans in Beijing( x 2=52.5,P<0.01)> Uigur( x 2=9.3,P<0.01) Muslim population in china ( x 2-12.2,P<0.01 )> Mongolians( x2=14.2,P<.01) .(4)Analysis of interaction between factors showed that: combination of MS A2756G and MTHFR C677T polymorphism on the risk of NTDs reveal there was synergistic action between the two polymorphism (Attributable Proportions of Interaction: API-0.41,the Synergy Index S=2.02), There was negative interaction between the polymorphism of MTHFR C677T and fresh vegetable (API=-0.44,S=0.46), Fresh vegetable could decrease the risk of fetal NTDs. Probably there was no interaction between the polymorphism of MTHFR C677T and germinated potato(API=0.05,S=1.05).Conclusion: It was suggested that not mother MS but MTHFR genetic polymorphism was one of the independent genetic risk factors of offspring NTDs. Higher T Allele frequency of MTHFR among Hans of Shanxi province than other areas was probably the main genetic cause of NTDs highest incidence rate. Taking fresh vegetable and fruit was environmental protective factor, which could decrease the risk of NTDs. While eating germinated potato was environmental risk factor. |
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