表皮生长因子基因遗传变异与非综合征型唇腭裂的研究

Association of epidermal growth factor genetic polymorphisms and non-syndromic orofacial clefts

目的探讨表皮生长因子启动子区多态性位点G61A与我国华东地区汉族人群非综合征型唇腭裂的相关性。方法病例组选取2008年8月—2009年5月期间在南京医科大学附属口腔医院唇腭裂外科病房住院的非综合征型唇腭裂患者139名,对照组选自同期在南京市儿童医院门诊就诊的健康儿童,无唇腭裂,无全身系统疾病或先天畸形。两组人群年龄、性别匹配。使用聚合酶链反应-限制性片段长度多态性对表皮生长因子G61A多态位点进行基因分型。结果在对照组中,3种基因型的频率分布符合Hardy-Weinberg遗传平衡定律(P=0.17)。总唇腭裂组与对照组基因型以及等位基因频率分布无显著性差异。与野生纯合子GG基因型相比,杂合突变型AG、纯合突变型AA以及总突变型(AG/AA)均与非综合征型唇腭裂的发病风险无显著性关联(AA基因型的OR=0.97,95%CI=0.42-2.22;AG基因型的OR=0.97,95%CI=0.56-1.67;AG/AA基因型的OR=0.97,95%CI=0.59-1.60)。进一步分组分析发现:AG基因型能够显著降低个体罹患腭裂的发病风险(AA基因型的OR=0.25,95%CI=0.07-0.90)。结论表皮生长因子G61A遗传变异可能是个体罹患单纯腭裂的易感因素之一。

Objective To determine the association of epidermal growth factor（EGF）,G61A polymorphisms with non-syndromic orofacial clefts（NOSC） susceptibility in a Chinese Han population.Methods 139 NSOC cases without the presence of associated congenital anomalies or syndromes and 107 healthy controls,frequency-matched to the cases on sex,age,were consecutively recruited from the Affiliated Stomatological Hospital of Nanjing Medical University and Nanjing Children＇s Hospital,from August 2008 to May 2009.The EGF G61A was genotyped by polymerase chain reaction-restriction fragment length polymorphism（PCR-RFLP）.Results The observed genotype frequencies in controls were in Hardy-Weinberg equilibrium（P = 0.17）.The genotype and allele frequencies in all cleft cases were similar to those in the controls.Non-significant associations were observed between the variant genotypes and NSOC risk（AA versus GG,OR = 0.97,95% CI = 0.42-2.22;AG versus GG,OR = 0.97,95% CI = 0.56-1.67;AA/AG versus GG,OR = 0.97,95% CI = 0.59-1.60）.When all cleft cases were subsequently stratified into three groups（i.e.CLO,CLP and CPO）,AA genotype significantly decreased the risk of CPO（OR = 0.25,95% CI = 0.07-0.90）.Conclusion EGF promoter SNP G61A may modify the risk of CPO in a Chinese Han population.