邵帅 张莉 刘华

[摘要]目的：分析p53基因单核苷酸多态性（SNPs）位点的多态性，探究云南汉族非综合征性唇腭裂与p53基因的相关性。方法：选取2016年1月-2018年12月于笔者医院就诊的非综合征性唇腭裂患儿100例为试验组，选取医院同期无先天性畸形正常患儿100例为对照组。采用Taqman探针荧光定量PCR法对p53基因的SNPs位点rs12947788和rs1042522进行基因分型，并用χ2检验和Logistic回归分析多态位点与非综合征性唇腭裂的相关性。结果：p53的基因SNPs位点rs12947788的等位基因变体A携带者（AA+GA vs GG）发生非综合征性唇腭裂的风险增加（OR=1.393，95%CI 1.030～1.884，P=0.032）。rs1042522（CC vs CG+GG）增加吸烟者母亲生下NSCL/P患儿的风险（OR=2.561，95% CI=1.146～5.721，P=0.022）。rs12947788（AA+GA vs GG）可明显增加有饮酒史母亲（OR=3.235，95%CI=1.158～9.040，P=0.025）生下NSCL/P患儿的风险。结论：云南汉族人群非综合征性唇腭裂与p53基因rs1042522、rs12947788多态具有一定的相关性。

[关键词]非综合征性唇腭裂;抑癌基因p53;基因多态性;相关性

Abstract： Objective  The single nucleotide polymorphism （SNPs） of p53 gene was analyzed to explore the correlation between p53 gene and non-syndromic cleft lip and palate of han nationality in yunnan province. Methods  A total of 100 children with non-syndromic cleft lip and palate admitted to our hospital from January 2016 to December 2018 were selected as the experimental group， and 100 children without congenital malformation during the same period in our hospital were selected as the control group. Taqman probe fluorescence quantitative PCR was used to genotype p53 SNPs sites rs12947788 and rs1042522， and the correlation between polymorphism sites and non-syndromic cleft lip and palate was analyzed by χ2 test and logistic regression. Results  Carriers of allele A of p53 SNPs rs12947788 （AA+GA vs GG） have an increased risk of developing non-syndromic cleft lip and palate （OR=1.393， 95%CI 1.030～1.884， P=0.032）. Rs1042522 （CC vs CG+GG） increased the risk of NSCL/P in children born to mothers of smokers （OR=2.561， 95% CI=1.146～5.721， P=0.022）. Rs12947788 （AA+GA vs GG） significantly increased the risk of NSCL/P in children born to mothers with drinking history （OR=3.235， 95%CI=1.158～9.040， P=0.025）. Conclusion  There is a certain correlation between non-syndromic cleft lip and palate and p53 gene rs1042522 and rs12947788 polymorphism in yunnan han population.

Key words： nonsyndromic cleft lip with or without cleft palate（NSCL/P）; tumor suppressor gene p53; gene polymorphism; garrelation

非綜合征性唇腭裂唇腭裂（Nonsyndromic cleft lip with or without cleft palate，NSCL/P）是临床外科最常见的先天性出生缺陷之一，指不伴发其他系统器官畸形的不属于任何综合征性唇腭裂的唇裂、腭裂的总称[1-3]。非综合征性唇腭裂在世界范围内发病率约为1‰～2‰[4]，中国地区的发病率约为1.42‰[5]，位列我国新生儿出生缺陷病第2位，具有明显的种族和地域差异。NSCL/P是一种由多种因素造成的复杂疾病，学者们一般都认为是基因和环境共同作用下的结果，与妊娠期吸烟[6]、符合维生素补充[7]、饮酒[8]以及基因多态性[9]等因素密切相关。目前有大量关于基因多态性与非综合征性唇腭裂相关的研究，干扰素调节因子-6（Interferon regulatory factor-6，IRF-6）基因和5，10-亚甲基四氢叶酸还原酶（Methylenetetrahydrofolate reductase，MTHFR）基因是学者们最主要的研究对象[10-11]。……