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.     

IRF6基因rs2235371位点多态性与非综合征性唇裂伴或不伴腭裂的相关性研究

目的 探讨干扰素调节因子6 (interferon regulatory factor 6,IRF6)基因rs2235371位点820G＞A单核苷酸多态性与非综合征性唇裂伴或不伴腭裂(nonsyndromic cleft lip with or without cleft palate,NSCL士P)的相关性.方法 收集106例患者及其父母以及129名对照及其父母的核心家庭标本,用聚合酶链反应-限制性片段长度多态性的方法进行IRF6基因rs2235371位点单核苷酸多态性检测;用人群关联研究、传递不平衡检验(transmission disequilibrium test,TDT)、单倍型相对风险率(haplotype-based haplotype relative risk,HHRR)、家系为基础的关联检验(family-based association tests,FBAT)等方法进行统计分析.结果 病例组与对照组相比,子代的基因型分布差异无统计学意义(P＞0.05),而等位基因频率比较差异有统计学意义(P＜0.05);母亲组基因型分布差异有统计学意义(P＜0.05);按唇腭裂类型分类后,单纯唇裂组子代基因型分布和等位基因的频率与对照组相比差异均有统计学意义(P＜0.05);而唇腭裂组基因型分布和等位基因频率差异均无统计学意义(P＞0.05).传递不平衡检验提示,rs2235371位点的G等位基因在NSCL±P核心家庭中存在传递不平衡(x2=5.56,P=0.024).HHRR检验x2=5.115,P=0.024,OR=1.674,95％CI:1.069～2.621;FBAT检验Z=2.218,P=0.027.结论 在中国北方人群中IRF6基因rs2235371位点突变与非综合征性唇腭裂存在关联.     

非综合征型唇裂伴或不伴腭裂的遗传方式

目的 为探讨非综合征型唇裂伴或小伴腭裂的遗传方式,对其高发家系进行遗传学研究. 方法 采用分离分析法和多基因阈值理论分析法对37个非综合征型唇裂伴或不伴腭裂的高发家系进行分析. 结果先证者的亲属患病率分别是一级亲属为29.89%(26/87),二级亲属为2.70%(4/148);其亲属发病率高低与血缘关系近远相关,与先让者血缘关系越近的亲属患病率越高;非综合征型唇裂伴或不伴腭裂的遗传方式不同于常染色体单基因显性、隐性遗传及性连锁遗传,而符合多基因遗传,其一级、二级亲属加权平均遗传度为(148.40±8.20)%. 结论非综合征型唇裂伴或不伴腭裂的遗传方式为多基因遗传.     

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.     

非综合征型唇腭裂易感基因多态性研究进展

非综合征型唇裂伴或不伴腭裂(nonsyndromic cleft lip with or without cleft palate,NSCL/P;简称为非综合征型唇腭裂)是指不伴发其他系统畸形的不属任何综合征的唇裂、唇裂合并腭裂的总称,这是一种常见的颌面部先天畸形[1].文献报道NSCI/P发病率为1/700 [2],不同种族和地域发病率有很大差异,其中亚洲黄种人最高、欧洲白种人次之、非洲黑种人最低.在我国NSCL/P发病率高居出生缺陷前列,远远高于世界平均水平.NSCL/P不仅造成患者面部畸形,而且还影响患者的语言、听力,甚至会影响患者的心理健康,给患者的家庭和社会都带来了严重的负担.而NSCI/P的治疗又是一个多学科联合的过程,尽管如此,大部分NSCL/P病例都不能完全治愈.因此寻找该病的病因,进而找到有效的预防手段显得非常重要.     

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.     

MTHFR基因C677T多态性与非综合征型唇腭裂的相关性研究

目的：探讨MTHFR基因C677T多态性与非综合征型唇腭裂（nonsyndromic cleft lip with or without cleft pa late,NSCL/P）相关性。方法：收集97个核心家庭和104个对照家庭,用聚合酶链式反应-限制性片段长度多态性方法,进行MTHFR基因C677T位点多态性检测;用人群关联研究、传递不平衡检验（transmission-disequlibrium test, TDT）、单倍型相对风险率（haplotype-based haplotype relative risk, HHRR）、家系为基础的关联检验（family-based association test, FBAT）等进行统计分析。结果：人群关联研究分析表明,子代、父亲、母亲的病例组和对照组之间基因型和等位基因的分布差异无统计学意义（P>0.05）;子代、父亲、母亲组,CT基因型携带者相对于CC基因型携带者的OR分别为1.02(95%CI 0.47~2.21)、0.62(95%CI 0.29~1.32)、0.66(95%CI 0.31~1.40);TT基因型携带者相对于CC基因型携带者的OR分别为1.10(95%CI 0.44~2.74)、0.95(95%CI 0.39~2.32)、0.68(95%CI 0.28~1.66);T相对于C基因的OR分别为1.07(95%CI 0.72~1.58)、0.98(95%CI 0.66~1.46)、0.83(95%CI 0.56~1.24)。携带有突变基因T并不能增加患NSCL/P的危险。病例组核心家庭分析表明,TDT检验χ²=1.817,P>0.05;HHRR检验χ²=1.76,P>0.05;FBAT检验Z=1.348,P>0.05。结论：没有发现MTHFR C677T 多态性和NSCLP无关联性,该基因位点的变异可能不会导致中国东北地区人群NSCLP的发生。