| Objectives: The purpose was to find out some suspectable risk factors (including genetic, environmental, nutritious factors) of neural tube defects (NTDs) in Shanxi Province where the incidence of NTDs is the highest in China. Meanwhile, it was explored that the correlation between plasma cell membrane glycoprotein-1(PC-1) gene, 5,10-methylenetetrahydrofolate reductase (MTHFR) gene in mother and susceptibility to NTDs in offspring. The interactions among these risk factors were analyzed and the functions of these factors were detected in offspring NTDs. Methods: 1:1 matched case-control study was used. Objects were chose from 25 hospitals in 6 regions with high incidence of NTDs in Shanxi Province. All the objects were divided into two groups: 99 deliveries with NTDs as a case group and 99 deliveries with normal newborns as a control group. All the objects were investigated in uniform questionnaires about suspec-table risk factors for NTDs and were genotyped for PC-1 K121Q and MTHFR C667T polymorphism by (polymerase chain reaction restriction fragment length polymorphism analysis, PCR-RFLP) method. All the data were analyzed by SPSS10.0 statistical software.The risk factors of NTDs were analyzed by the conditional Logistic regression. Results: (1) Comparing PC-1 gene frequency between the two groups, it was showed that only two genotypes were found in PC-1 K121Q. The frequencies of K121K, K121Q were respectively 90.9% and 9.1% in case group, 93.9% and 6.1% in control group (χ~2=0.65,P>0.10). Allele frequencies of K and Q were respectively 95.5 % and 4.5% in case group, 97.0% and 3.0% in control group (χ~2=0.62,P>0.10). The discrepancy was remarkable. (2) Comparing MTHFR gene frequency between the two groups, it was showed that three genotypes were found in MTHFR C677T. The frequencies of C677C, C677T, T677T were 14.1%, 50.5%, 35.4% in case group respectively, 34.3%, 48.5%, 17.2% in control group. There was significant difference between two groups at 0.01 level (χ~2=14.61,P<0.01). Furthermore, with the increase of the number of allele T in mother, the risk of offspring NTDs was elevated. Allele frequencies of C and T were respectively 39.4%, 60.6% in case group, 58.6% and 41.4% in the control group. The difference was remarkable between two groups.(χ~2=14.53,P<0.01). Comparing MTHFR gene among population in different regions and races, it was showed that there were significant difference of the distribution of MTHFR genotype frequency among Han nationality in Shanxi, Han nationality in Guangdong and Peking and Black people (P<0.01), and Han nationality in Shanxi comparing with Han nationality from northern China, Mongol and Caucasian, the discrepancy was unremarkable (P>0.05). In addition, so was the distribution of allele frequency. The distribution of MTHFR genotype and allele frequency was coincident with the distribution of incidence of NTDs. (3) By univariate conditional Logistic regression analysis, it was indicated that 15 factors were correlated with NTDs (P<0.05) in the level α=0.05. By multi-variables conditional Logistic regression analysis, it was showed that there were four factors were correlated with NTDs: frequency of pregnancy (OR=2.87), contacting chemical combination in early pregnancy (OR=16.18), taking germinated potato frequently (OR=4.66) and MTHFR C677T mutation (OR=2.13). (4) Analyzing interaction between factors, it was showed that there was negative interaction between the polymorphism of MTHFR C677T and fresh fruits (attributable proportions of interaction (API)=-0.43, the synergy index S, (S)=0.29). The risk of fetal NTDs may be decreased by fresh fruits. There was synergistic action between the polymorphism of MTHFR C677T andgerminated potatoes (API=0.33,S=1.58). Combinating polymorphism of PC-1 K121Q and MTHFR C677T on the risk of NTDs, there was no evidence of interaction, but as the number of mutated alley adds, the OR increases accordingly. Conclusions: It is suggested that not PC-1 K121Q but MTHFR C677T polymorphism in mother is one independent genetic risk factors of offsp...
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