Introduction: Non-Syndromic Clefts Lip-Palates (NSCLP/CP) are most common congenital malformation in the world, with very important psychic and social impact. Formation of NSCLP/CP arises from the interaction of envir...Introduction: Non-Syndromic Clefts Lip-Palates (NSCLP/CP) are most common congenital malformation in the world, with very important psychic and social impact. Formation of NSCLP/CP arises from the interaction of environmental and genetic factors. This paper provides a review of recent progress in defining the genetic causes of NSCLP. Methods: A literature review was conducted on the Medline data by searching for the following keywords: genes, non-syndromic cleft lip-palate, and genetics of clefts lip-palates, until January 2018. Results: Various genes are identified in different population and country, with the study using case parent’s trio. The aim of this study contributes to review relative gene which has been identify in non-syndromic cleft lip and palate, and to help to have a better understanding of the inheritance pattern of this pathology and the prevention of genetic disease. Conclusion: Although three major genes have been confirmed, the genetic research is necessary to provide an understanding of the pathophysiology of the clefts lip-palates.展开更多
目的:探索亚裔人群中转化生长因子β(transforming growth factor-β,TGF-β)信号通路基因多态性与非综合征型唇裂合并或不合并腭裂(non-syndromic cleft lip with or without cleft palate,NSCL/P)的关联及可能存在的基因-基因、基因-...目的:探索亚裔人群中转化生长因子β(transforming growth factor-β,TGF-β)信号通路基因多态性与非综合征型唇裂合并或不合并腭裂(non-syndromic cleft lip with or without cleft palate,NSCL/P)的关联及可能存在的基因-基因、基因-环境交互作用。方法:选取1038个NSCL/P核心家系作为研究对象。对TGF-β信号通路上的10个基因的343个单核苷酸多态性(single nucleotide polymorphism,SNP)位点进行了传递不平衡检验(transmission disequilibrium test,TDT),采用条件Logistic回归模型进行基因-基因交互作用分析和基因-环境交互作用分析。研究收集的环境因素包括患儿母亲孕期吸烟、被动吸烟、乙醇摄入量以及维生素使用情况。由于患儿母亲孕期吸烟和饮酒暴露率较低(<3%),因此,仅对母亲孕期被动吸烟及补充多种维生素这两个环境因素与基因之间的交互作用进行了分析。采用Bonferroni法对结果进行多重检验校正,显著性的阈值设置为P=1.46×10-4。结果:共有4个基因的23个SNP位点与NSCL/P之间存在关联(P<0.05),但经过Bonferroni多重检验校正后,这些关联均未达到统计学显著性水平。经过Bonferroni多重检验校正之后,6对SNP[rs4939874(SMAD2)与rs1864615(TGFBR2),rs2796813(TGFB2)与rs2132298(TGFBR2),rs4147358(SMAD3)与rs1346907(TGFBR2),rs4939874(SMAD2)与rs1019855(TGFBR2),rs4939874(SMAD2)与rs12490466(TGFBR2),以及rs2009112(TGFB2)与rs4075748(TGFBR2)]存在显著的统计学交互作用(P<1.46×10-4),基因-环境交互作用的分析没有达到多重检验校正阈值的显著结果。结论:未发现TGF-β通路基因多态性与NSCL/P的关联,该通路上部分基因可能通过基因-基因交互作用影响NSCL/P的发病风险。未来仍需其他独立研究的证据支持,以进一步的探索其中潜在的生物学机制。展开更多
唇腭裂(cleft lip and palate, CLP)是最为普遍的先天性出生缺陷之一,在不同地区和不同人群中患病率有一定的差异性,男性患病率略高,发病机制复杂,还有待持续深入研究,目前观点认为遗传和环境因素的共同作用是导致其发病的主要原因。本...唇腭裂(cleft lip and palate, CLP)是最为普遍的先天性出生缺陷之一,在不同地区和不同人群中患病率有一定的差异性,男性患病率略高,发病机制复杂,还有待持续深入研究,目前观点认为遗传和环境因素的共同作用是导致其发病的主要原因。本文就非综合征型唇腭裂(non-syndromic cleft lip with or without cleft palate, NSCL/P)的相关基因学的研究方法、致病基因、基因与WNT信号通路之间的关联性、基因与环境因素交互作用及早期产前诊断方面,总结了近几年NSCL/P研究进展,为进一步研究NSCL/P病因及预防提供参考。展开更多
文摘Introduction: Non-Syndromic Clefts Lip-Palates (NSCLP/CP) are most common congenital malformation in the world, with very important psychic and social impact. Formation of NSCLP/CP arises from the interaction of environmental and genetic factors. This paper provides a review of recent progress in defining the genetic causes of NSCLP. Methods: A literature review was conducted on the Medline data by searching for the following keywords: genes, non-syndromic cleft lip-palate, and genetics of clefts lip-palates, until January 2018. Results: Various genes are identified in different population and country, with the study using case parent’s trio. The aim of this study contributes to review relative gene which has been identify in non-syndromic cleft lip and palate, and to help to have a better understanding of the inheritance pattern of this pathology and the prevention of genetic disease. Conclusion: Although three major genes have been confirmed, the genetic research is necessary to provide an understanding of the pathophysiology of the clefts lip-palates.
文摘目的:探索亚裔人群中转化生长因子β(transforming growth factor-β,TGF-β)信号通路基因多态性与非综合征型唇裂合并或不合并腭裂(non-syndromic cleft lip with or without cleft palate,NSCL/P)的关联及可能存在的基因-基因、基因-环境交互作用。方法:选取1038个NSCL/P核心家系作为研究对象。对TGF-β信号通路上的10个基因的343个单核苷酸多态性(single nucleotide polymorphism,SNP)位点进行了传递不平衡检验(transmission disequilibrium test,TDT),采用条件Logistic回归模型进行基因-基因交互作用分析和基因-环境交互作用分析。研究收集的环境因素包括患儿母亲孕期吸烟、被动吸烟、乙醇摄入量以及维生素使用情况。由于患儿母亲孕期吸烟和饮酒暴露率较低(<3%),因此,仅对母亲孕期被动吸烟及补充多种维生素这两个环境因素与基因之间的交互作用进行了分析。采用Bonferroni法对结果进行多重检验校正,显著性的阈值设置为P=1.46×10-4。结果:共有4个基因的23个SNP位点与NSCL/P之间存在关联(P<0.05),但经过Bonferroni多重检验校正后,这些关联均未达到统计学显著性水平。经过Bonferroni多重检验校正之后,6对SNP[rs4939874(SMAD2)与rs1864615(TGFBR2),rs2796813(TGFB2)与rs2132298(TGFBR2),rs4147358(SMAD3)与rs1346907(TGFBR2),rs4939874(SMAD2)与rs1019855(TGFBR2),rs4939874(SMAD2)与rs12490466(TGFBR2),以及rs2009112(TGFB2)与rs4075748(TGFBR2)]存在显著的统计学交互作用(P<1.46×10-4),基因-环境交互作用的分析没有达到多重检验校正阈值的显著结果。结论:未发现TGF-β通路基因多态性与NSCL/P的关联,该通路上部分基因可能通过基因-基因交互作用影响NSCL/P的发病风险。未来仍需其他独立研究的证据支持,以进一步的探索其中潜在的生物学机制。
文摘唇腭裂(cleft lip and palate, CLP)是最为普遍的先天性出生缺陷之一,在不同地区和不同人群中患病率有一定的差异性,男性患病率略高,发病机制复杂,还有待持续深入研究,目前观点认为遗传和环境因素的共同作用是导致其发病的主要原因。本文就非综合征型唇腭裂(non-syndromic cleft lip with or without cleft palate, NSCL/P)的相关基因学的研究方法、致病基因、基因与WNT信号通路之间的关联性、基因与环境因素交互作用及早期产前诊断方面,总结了近几年NSCL/P研究进展,为进一步研究NSCL/P病因及预防提供参考。
