蛋氨酸合酶基因A275 6G位点多态性与非综合征型唇腭裂的关联性研究

Objective To study the association of the A2756G polymorphism of the methionine synthase (MS) gene with nonsyndromie cleft lip with or without cleft palate (NSCL/P) in Chinese. Methods Ninety-seven NSCL/P case-parent triads were selected as the case group. One hundred and four healthy subjects and their biological parents were selected as control group. For all subjects the A2756G polymorphism of the MS gene was examined by PCR-RFLP method. Results There was no statistical difference in genotype and allele frequencies for MS A2756G variants among family members between case group and control group. The GG genotype was not detected in the offsprings and mothers. The odds ratio and confidence interval of genotype AG in offspring, father and mother were 1.78(0.74-4.34), 0.80(0. 36-1.79) and 1.26(0. 54-2.93) respectively. The odds ratio and confidence interval of allele G in offspring, father and mother were 1.70(0.78-3.73), 0. 88(0. 49-1. 75) , and 1.23(0.59-2.60) respectively. The G allele did not increase the risk of NSCL/P. Transmission disequilibrium test (TDT) analysis yielded no evidence of linkage disequilibrium (χ2=0.034,P>0. 05). The results of haplotype-based haplotype relative risk (HHRR) analysis (χ2=0.03,P>0.05) and family-based association tests (FBAT) (Z=0. 186, P> 0.05) failed to show association between the MS A2756G variant and the risk of NSCL/P. Conclusion The A2756G polymorphism of the MS gene was not associated with NSCL/P in Chinese in the present study.     

蛋氨酸合酶基因A275 6G位点多态性与非综合征型唇腭裂的关联性研究

Objective To study the association of the A2756G polymorphism of the methionine synthase (MS) gene with nonsyndromie cleft lip with or without cleft palate (NSCL/P) in Chinese. Methods Ninety-seven NSCL/P case-parent triads were selected as the case group. One hundred and four healthy subjects and their biological parents were selected as control group. For all subjects the A2756G polymorphism of the MS gene was examined by PCR-RFLP method. Results There was no statistical difference in genotype and allele frequencies for MS A2756G variants among family members between case group and control group. The GG genotype was not detected in the offsprings and mothers. The odds ratio and confidence interval of genotype AG in offspring, father and mother were 1.78(0.74-4.34), 0.80(0. 36-1.79) and 1.26(0. 54-2.93) respectively. The odds ratio and confidence interval of allele G in offspring, father and mother were 1.70(0.78-3.73), 0. 88(0. 49-1. 75) , and 1.23(0.59-2.60) respectively. The G allele did not increase the risk of NSCL/P. Transmission disequilibrium test (TDT) analysis yielded no evidence of linkage disequilibrium (χ2=0.034,P>0. 05). The results of haplotype-based haplotype relative risk (HHRR) analysis (χ2=0.03,P>0.05) and family-based association tests (FBAT) (Z=0. 186, P> 0.05) failed to show association between the MS A2756G variant and the risk of NSCL/P. Conclusion The A2756G polymorphism of the MS gene was not associated with NSCL/P in Chinese in the present study.     

蛋氨酸合酶基因A275 6G位点多态性与非综合征型唇腭裂的关联性研究

Objective To study the association of the A2756G polymorphism of the methionine synthase (MS) gene with nonsyndromie cleft lip with or without cleft palate (NSCL/P) in Chinese. Methods Ninety-seven NSCL/P case-parent triads were selected as the case group. One hundred and four healthy subjects and their biological parents were selected as control group. For all subjects the A2756G polymorphism of the MS gene was examined by PCR-RFLP method. Results There was no statistical difference in genotype and allele frequencies for MS A2756G variants among family members between case group and control group. The GG genotype was not detected in the offsprings and mothers. The odds ratio and confidence interval of genotype AG in offspring, father and mother were 1.78(0.74-4.34), 0.80(0. 36-1.79) and 1.26(0. 54-2.93) respectively. The odds ratio and confidence interval of allele G in offspring, father and mother were 1.70(0.78-3.73), 0. 88(0. 49-1. 75) , and 1.23(0.59-2.60) respectively. The G allele did not increase the risk of NSCL/P. Transmission disequilibrium test (TDT) analysis yielded no evidence of linkage disequilibrium (χ2=0.034,P>0. 05). The results of haplotype-based haplotype relative risk (HHRR) analysis (χ2=0.03,P>0.05) and family-based association tests (FBAT) (Z=0. 186, P> 0.05) failed to show association between the MS A2756G variant and the risk of NSCL/P. Conclusion The A2756G polymorphism of the MS gene was not associated with NSCL/P in Chinese in the present study.     

蛋氨酸合酶基因A275 6G位点多态性与非综合征型唇腭裂的关联性研究

Objective To study the association of the A2756G polymorphism of the methionine synthase (MS) gene with nonsyndromie cleft lip with or without cleft palate (NSCL/P) in Chinese. Methods Ninety-seven NSCL/P case-parent triads were selected as the case group. One hundred and four healthy subjects and their biological parents were selected as control group. For all subjects the A2756G polymorphism of the MS gene was examined by PCR-RFLP method. Results There was no statistical difference in genotype and allele frequencies for MS A2756G variants among family members between case group and control group. The GG genotype was not detected in the offsprings and mothers. The odds ratio and confidence interval of genotype AG in offspring, father and mother were 1.78(0.74-4.34), 0.80(0. 36-1.79) and 1.26(0. 54-2.93) respectively. The odds ratio and confidence interval of allele G in offspring, father and mother were 1.70(0.78-3.73), 0. 88(0. 49-1. 75) , and 1.23(0.59-2.60) respectively. The G allele did not increase the risk of NSCL/P. Transmission disequilibrium test (TDT) analysis yielded no evidence of linkage disequilibrium (χ2=0.034,P>0. 05). The results of haplotype-based haplotype relative risk (HHRR) analysis (χ2=0.03,P>0.05) and family-based association tests (FBAT) (Z=0. 186, P> 0.05) failed to show association between the MS A2756G variant and the risk of NSCL/P. Conclusion The A2756G polymorphism of the MS gene was not associated with NSCL/P in Chinese in the present study.     

蛋氨酸合酶基因A275 6G位点多态性与非综合征型唇腭裂的关联性研究

Objective To study the association of the A2756G polymorphism of the methionine synthase (MS) gene with nonsyndromie cleft lip with or without cleft palate (NSCL/P) in Chinese. Methods Ninety-seven NSCL/P case-parent triads were selected as the case group. One hundred and four healthy subjects and their biological parents were selected as control group. For all subjects the A2756G polymorphism of the MS gene was examined by PCR-RFLP method. Results There was no statistical difference in genotype and allele frequencies for MS A2756G variants among family members between case group and control group. The GG genotype was not detected in the offsprings and mothers. The odds ratio and confidence interval of genotype AG in offspring, father and mother were 1.78(0.74-4.34), 0.80(0. 36-1.79) and 1.26(0. 54-2.93) respectively. The odds ratio and confidence interval of allele G in offspring, father and mother were 1.70(0.78-3.73), 0. 88(0. 49-1. 75) , and 1.23(0.59-2.60) respectively. The G allele did not increase the risk of NSCL/P. Transmission disequilibrium test (TDT) analysis yielded no evidence of linkage disequilibrium (χ2=0.034,P>0. 05). The results of haplotype-based haplotype relative risk (HHRR) analysis (χ2=0.03,P>0.05) and family-based association tests (FBAT) (Z=0. 186, P> 0.05) failed to show association between the MS A2756G variant and the risk of NSCL/P. Conclusion The A2756G polymorphism of the MS gene was not associated with NSCL/P in Chinese in the present study.     

蛋氨酸合酶基因A275 6G位点多态性与非综合征型唇腭裂的关联性研究

Objective To study the association of the A2756G polymorphism of the methionine synthase (MS) gene with nonsyndromie cleft lip with or without cleft palate (NSCL/P) in Chinese. Methods Ninety-seven NSCL/P case-parent triads were selected as the case group. One hundred and four healthy subjects and their biological parents were selected as control group. For all subjects the A2756G polymorphism of the MS gene was examined by PCR-RFLP method. Results There was no statistical difference in genotype and allele frequencies for MS A2756G variants among family members between case group and control group. The GG genotype was not detected in the offsprings and mothers. The odds ratio and confidence interval of genotype AG in offspring, father and mother were 1.78(0.74-4.34), 0.80(0. 36-1.79) and 1.26(0. 54-2.93) respectively. The odds ratio and confidence interval of allele G in offspring, father and mother were 1.70(0.78-3.73), 0. 88(0. 49-1. 75) , and 1.23(0.59-2.60) respectively. The G allele did not increase the risk of NSCL/P. Transmission disequilibrium test (TDT) analysis yielded no evidence of linkage disequilibrium (χ2=0.034,P>0. 05). The results of haplotype-based haplotype relative risk (HHRR) analysis (χ2=0.03,P>0.05) and family-based association tests (FBAT) (Z=0. 186, P> 0.05) failed to show association between the MS A2756G variant and the risk of NSCL/P. Conclusion The A2756G polymorphism of the MS gene was not associated with NSCL/P in Chinese in the present study.     

蛋氨酸合酶基因A275 6G位点多态性与非综合征型唇腭裂的关联性研究

Objective To study the association of the A2756G polymorphism of the methionine synthase (MS) gene with nonsyndromie cleft lip with or without cleft palate (NSCL/P) in Chinese. Methods Ninety-seven NSCL/P case-parent triads were selected as the case group. One hundred and four healthy subjects and their biological parents were selected as control group. For all subjects the A2756G polymorphism of the MS gene was examined by PCR-RFLP method. Results There was no statistical difference in genotype and allele frequencies for MS A2756G variants among family members between case group and control group. The GG genotype was not detected in the offsprings and mothers. The odds ratio and confidence interval of genotype AG in offspring, father and mother were 1.78(0.74-4.34), 0.80(0. 36-1.79) and 1.26(0. 54-2.93) respectively. The odds ratio and confidence interval of allele G in offspring, father and mother were 1.70(0.78-3.73), 0. 88(0. 49-1. 75) , and 1.23(0.59-2.60) respectively. The G allele did not increase the risk of NSCL/P. Transmission disequilibrium test (TDT) analysis yielded no evidence of linkage disequilibrium (χ2=0.034,P>0. 05). The results of haplotype-based haplotype relative risk (HHRR) analysis (χ2=0.03,P>0.05) and family-based association tests (FBAT) (Z=0. 186, P> 0.05) failed to show association between the MS A2756G variant and the risk of NSCL/P. Conclusion The A2756G polymorphism of the MS gene was not associated with NSCL/P in Chinese in the present study.     

蛋氨酸合酶基因A275 6G位点多态性与非综合征型唇腭裂的关联性研究

Objective To study the association of the A2756G polymorphism of the methionine synthase (MS) gene with nonsyndromie cleft lip with or without cleft palate (NSCL/P) in Chinese. Methods Ninety-seven NSCL/P case-parent triads were selected as the case group. One hundred and four healthy subjects and their biological parents were selected as control group. For all subjects the A2756G polymorphism of the MS gene was examined by PCR-RFLP method. Results There was no statistical difference in genotype and allele frequencies for MS A2756G variants among family members between case group and control group. The GG genotype was not detected in the offsprings and mothers. The odds ratio and confidence interval of genotype AG in offspring, father and mother were 1.78(0.74-4.34), 0.80(0. 36-1.79) and 1.26(0. 54-2.93) respectively. The odds ratio and confidence interval of allele G in offspring, father and mother were 1.70(0.78-3.73), 0. 88(0. 49-1. 75) , and 1.23(0.59-2.60) respectively. The G allele did not increase the risk of NSCL/P. Transmission disequilibrium test (TDT) analysis yielded no evidence of linkage disequilibrium (χ2=0.034,P>0. 05). The results of haplotype-based haplotype relative risk (HHRR) analysis (χ2=0.03,P>0.05) and family-based association tests (FBAT) (Z=0. 186, P> 0.05) failed to show association between the MS A2756G variant and the risk of NSCL/P. Conclusion The A2756G polymorphism of the MS gene was not associated with NSCL/P in Chinese in the present study.     

蛋氨酸合酶基因A275 6G位点多态性与非综合征型唇腭裂的关联性研究

Objective To study the association of the A2756G polymorphism of the methionine synthase (MS) gene with nonsyndromie cleft lip with or without cleft palate (NSCL/P) in Chinese. Methods Ninety-seven NSCL/P case-parent triads were selected as the case group. One hundred and four healthy subjects and their biological parents were selected as control group. For all subjects the A2756G polymorphism of the MS gene was examined by PCR-RFLP method. Results There was no statistical difference in genotype and allele frequencies for MS A2756G variants among family members between case group and control group. The GG genotype was not detected in the offsprings and mothers. The odds ratio and confidence interval of genotype AG in offspring, father and mother were 1.78(0.74-4.34), 0.80(0. 36-1.79) and 1.26(0. 54-2.93) respectively. The odds ratio and confidence interval of allele G in offspring, father and mother were 1.70(0.78-3.73), 0. 88(0. 49-1. 75) , and 1.23(0.59-2.60) respectively. The G allele did not increase the risk of NSCL/P. Transmission disequilibrium test (TDT) analysis yielded no evidence of linkage disequilibrium (χ2=0.034,P>0. 05). The results of haplotype-based haplotype relative risk (HHRR) analysis (χ2=0.03,P>0.05) and family-based association tests (FBAT) (Z=0. 186, P> 0.05) failed to show association between the MS A2756G variant and the risk of NSCL/P. Conclusion The A2756G polymorphism of the MS gene was not associated with NSCL/P in Chinese in the present study.     

Parkin基因启动子区-258T/G多态性与广西地区散发性帕金森病的相关性分析

Objective To investigate the association between the-258T/G polymorphism.in the pro-moter of parkin gene and the risk for sporadic parkinson's disease (SPD) in Guangxi Province, and in relationto the age of onset, of PD patients. Methods PCR-RFLP and sequence analysis were used to determine thegenotype of-258T/G polymorphism between all patients and healthy controls. Results The G allele was morecommon in patients than controls (55.20%:43.33% ,x2=6.898, P<0.05, OR=1.61, 95% CI: 1.13 ～2.30). The frequency of GG genotype was higher in patients than in controls (28.00 %: 18.33%, x2=7.159, P<0.05, OR=2.75, 95% CI : 1.31 ～ 5.77). The frequency of TG + GG genotype was higher in pa-tients than in controls (82.40%:68.33%, x2=6.551, P<0.05, OR=2.17.95%CI: 1.20 ～3.93). Afterbeing stratified by onset age, the frequencies of the G allele and GG genotype were significantly higher in pa-tients with onset age over 50 years than those in controls respectively. On the other hand, the frequency was notsignificantly different between the younger onset PD patients and the controls. Conclusion The parkin promot-er-258T/G polymorphism might be a risk factor for PD in Guangxi Province, and the G allele was increasedwith increasing age.     

Maternal MTHFR variant forms increase the risk in offspring of isolated nonsyndromic cleft lip with or without cleft palate

The pathogenesis of cleft lip with or without cleft palate (CL/P) is complex; its onset could be due to the interaction of various genetic and environmental factors. Recently MTHFR functional polymorphisms were found to increase the risk of this common malformation; however, this finding is still debated. We investigated 110 sporadic CL/P patients, their parents and 289 unrelated controls for c.665C>T (commonly known as 677C>T; p.Ala222Val) and c.1286A>C (known as 1298A>C; p.Glu429Ala) polymorphism in the MTHFR gene. Transmission disequilibrium test (TDT) showed no distortion in allele transmission. Nevertheless, association studies revealed significant differences in allele frequencies between mothers of CL/P patients and controls. This work supports the hypothesis that a lower MTHFR enzyme activity in pregnant women, mostly related to the c.665C>T variant form, is responsible for a higher risk of having CL/P affected offspring.     

唇腭裂相关基因研究进展

唇腭裂是一种常见的先天性畸形,其病因非常复杂,目前倾向认为是由多种基因和环境因素共同作用的结果。常见的引起唇腭裂相关的基因有TGFA,TGFβ3, BCL3, F13A等;环境因素在唇腭裂发生中的遗传修饰作用也很重要,主要的环境激发因素包括致畸因子（如烟草、酒精、糖皮质激素等）、感染和营养缺乏。基于基因打靶技术建立的鼠基因敲除模型很好地模拟了人类疾病的表现型,成为研究唇腭裂的一种强有力手段。     

Informative morphogenetic and phenogenetic variants in children with cleft lip/cleft palate

In 230 patients with nonsyndromic cleft lip/cleft palate (138 boys and 92 girls) and in 226 age related healthy children (137 boys and 89 girls) informative morphogenetic and phenogenetic variants (IMV and PHV, respectively) were investigated. There was no difference between the number of IMVs between both groups (χ² = 5.89; d.f. = 3; α > 0.70). This finding is in line with the hypothesis that facial cleft disorders occur during blastogenesis, whereas IMVs and PHVs are typical patterns of the embryo- and fetogenesis. The anthropometric findings are contradictory. In a few non-craniofacial phenogenetic variants significant differences were found between the patients and the healthy children. Intrinsic factors or secondary sequelae of the primary defect might additionally act in the morphological fine tuning of children with single cleft lip/cleft palate. © 1996 Wiley-Liss, Inc.