IRF6基因rs642961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

Relationship between genetic polymorphisms of IRF6 rs642961 and nonsysdromic cleft lip with or without cleft palate

目的探讨中国北方人群干扰素调节因子6(IRF6)基因rs642961位点多态性与非综合征性唇裂伴或不伴腭裂(NSCL±P)的相关性。方法收集中国北方人群88个病例核心家庭和116个正常儿童作对照,用四引物扩增受阻突变体系聚合酶链反应(tetra-primer ARMS-PCR)的方法,进行IRF6基因rs642961检测;用人群关联研究、传递不平衡检验(TDT)、单倍型相对风险率(HHRR)、家庭为基础的关联检验(family-based association test,FBAT)等进行统计分析。结果子代、父亲、母亲三个亚组人群的IRF6基因rs642961位点的基因型在NSCL±P组与对照组的分布差异具有统计学意义(P<0.05),OR值及其95%可信区间均不包含1,提示IRF6基因rs642961位点的变异能增加NSCL±P发病的危险。核心家庭资料TDT和HHRR的结果均显示有统计学差异(P<0.05),FBAT分析提示可能存在加性传递模式(P<0.05),进一步支持IRF6基因rs642961位点的突变和NSCL±P发生相关。结论在中国北方人群中,IRF6基因rs642961位点多态性与NSCL±P发病相关。

Objective To explore the relationship between polymorphism of interferon regulatory factor 6（ IRF6） gene rs642961 locus and nonsyndromic cleft lip with or without cleft palate（ NSCL ± P）. Methods There were 88 NSCL ± P nuclear families and 116 healthy people as control recruited from Chinese northern area. The polymorphism of IRF6rs642961 locus was detected by tetra-primer amplification refractory mutation systempolymerase chain reaction（ tetra-primer ARMS-PCR）. Case-control analysis,transmission-disequilibrium test（ TDT）,haplotype-based haplotype relative risk analysis（ HHRR） and family-based association test（ FBAT） were carried out. Result There was significant difference in rs642961 of IRF6 locus between the NSCL ± P group and control group,whether in children or parents（ P〈0. 05）. The odds ratio（ OR） of AG and AA versus GG is above one,and its 95% confidence interval did not include 1 in offspring,father and mother group,which meant genetic variant of rs642961 of IRF6 could increase the risk of occurrence of NSCL ± P. The allele transmission disequilibrium for rs642961 of IRF6 variant in NSCL ± P families was found by TDT analysis（ P〈0. 05）. HHRR calculation also showed that there was association between the genetic variant and the occurrence of NSCL ± P（ P〈0. 05）. While FBAT test showed that there was relationship between the genetic variant and the occurrence of NSCL ± P in addictive model.Conclusion Polymorphism IRF6 gene locus is associated with NSCL ± P in northern Chinese population.