基于核心家系的CES1基因多态性与非综合征型唇腭裂易感性的关联分析

目的：利用以核心家系为基础的关联分析,探讨唇腭裂候选基因羧酸酯酶1 （CES1）基因多态性与非综合征型唇腭裂（NSCL/P）易感性的关系.方法：收集12例完整的患儿-健康父母3人核心家系（包含12例患儿组,24例父母组）作为研究对象,运用家系分析（FBAT）软件分析CES1基因多态性与NSCL/P易感性之间的关联性.结果：在FBAT检验的累加模式、显性模式以及隐性模式下均未显示CES1单核苷酸多态性位点（SNP）等位基因的分布与NSCL/P存在遗传学关联,FBAT累加模式下（A：Z=-0.229,P=0.819;G：Z=0.229,P=0.819）显性模式下（G：Z=-0.333,P=0.739）隐性模式下（A：Z=0.333,P=0.739）.结论：虽然全基因关联性分析发现参与肝脏解毒功能主要基因CES1与唇腭裂的发生有关,但是通过FBAT分析CES1等位基因与唇腭裂无遗传学关联.该基因突变可能是随机产生的,具有这些基因突变的个体,可能对环境因素中化学毒物的敏感性增加,导致唇腭裂的产生.

FAMILY-BASED ASSOCIATION STUDY OF CES1 GENE POLYMORPHISMS IN NSCL/P

Objective：We used family-based associated test （FBAT） to investigate the relationship between CES1 polymorphisms and susceptibility of NSCL/P.Methods：Thirty-six study subjects 12 case-parent trio nuclear families were recruited in the study （include 12 cases and 24 cases parents group）.The genotype data were analyzed with FBAT software to check linkage and association between the CES1 and susceptibility of NSCL/P.Results：The result of FBAT including additive model,dominant model and recessive model showed the different alleles of CES1 had no correlation with the onset of NSCL/P.FBAT additive model （A：Z =-0.229,P =0.819; G：Z =0.229,P =0.819） dominant model （G：Z =-0.333,P =0.739） recessive model （A：Z =0.333,P =0.739）.Conclusion：Although genome wide association study found that CES1 is associated with the occurrence of cleft lip and palate,but these is no evidence of an association between CES1 gene and hereditary of NSCL/P.The gene mutation may be randomly generated.The individuals with these mutations may increase susceptibility to environmental factors or chemical toxins,resulting in NSCL/P.