ELL2基因多态性与涎腺多形性腺瘤易感性的相关性分析

Association between ELL2 polymorphism and susceptibility to pleomorphic adenoma of salivary gland

目的分析ELL2基因1119T>C多态性与涎腺多形性腺瘤易感性之间的相关性。方法绘制涎腺多形性腺瘤家系,对涎腺多形性腺瘤家系中5个成员的ELL2基因外显子进行测序;采用病例对照研究,将2016年1月-2020年7月就诊于山西白求恩医院口腔颌面外科的112例涎腺多形性腺瘤患者作为病例组,以年龄、性别为匹配条件,将2019年1月-2020年1月该院176名健康体检者作为对照组。高分辨熔解曲线(HRM)检测两组ELL2基因1119T>C多态性;采用χ2检验分析基因多态性与涎腺多形性腺瘤发生之间的相关性,分层分析评估吸烟与基因型的协同作用;并采用实时定量反转录聚合酶链反应(RT-PCR)检测不同基因型个体ELL2的表达水平。结果涎腺多形性腺瘤家系中ELL2基因第8外显子存在1119T>C多态性位点。病例对照研究结果显示,涎腺多形性腺瘤患者该位点纯合子CC基因频率明显高于对照组(24.1%vs.11.9%,P=0.002)。纯合子CC与涎腺多形性腺瘤发生风险增加相关(OR=3.059,95%CI 1.494~6.263)。分层分析显示,吸烟与1119C等位基因协同作用可增加涎腺多形性腺瘤发生的风险(OR=3.200,95%CI 1.460~7.014)。CC基因型个体ELL2 mRNA表达水平明显高于CT或TT基因型个体(P<0.05)。结论ELL2基因变异可能在涎腺多形性腺瘤的发生中起重要作用,吸烟联合1119C等位基因可增加涎腺多形性腺瘤的发病风险。

Objective To analyze the correlation between the ELL2 gene 1119 T>C polymorphism and the susceptibility to pleomorphic adenoma of the salivary gland.Methods The pedigree of the pleomorphic adenoma family of salivary gland was drawn.The exons of ELL2 gene in 5 members of salivary pleomorphic adenoma family were sequenced.A case-control study was conducted.One hundred and twelve patients with pleomorphic adenoma of the salivary gland who visited the Department of Oral and Maxillofacial Surgery of Shanxi Bethune Hospital from January 2016 to July 2020 were taken as case group,and 176 healthy examinees from January 2019 to January 2020 were taken as control group with age and sex as matching conditions.The 1119 T>C polymorphism of ELL2 genes in the two groups were detected with high resolution melting(HRM)curve.Chi-square test was adopted to analyze the correlation between gene polymorphism and the occurrence of pleomorphic adenoma of the salivary gland,stratified analysis was performed to evaluate the synergistic effect of smoking and genotype,and real time quantitative reverse transcription polymerase chain reaction(RT-PCR)was used to detect the expression level of ELL2 in individuals with different genotypes.Results The 1119 T>C polymorphism site existed in the exon 8 of ELL2 gene in a family with pleomorphic adenoma of salivary gland.The results of case-control study showed that the genotype frequency of homozygous CC was significantly higher in patients with pleomorphic adenoma of salivary gland than that in the controls(24.1%vs.11.9%,P=0.002).Homozygous CC was associated with increased risk for developing pleomorphic adenoma of salivary gland(OR=3.059,95%CI 1.494-6.263)in this cohort.Stratification analysis showed that smoking and 1119C allele cooperated to increase the risk of pleomorphic adenoma of salivary gland(OR=3.200,95%CI 1.460-7.014).The expression level of ELL2 mRNA in CC genotype was significantly higher than that in individuals with CT or TT genotype(P<0.05).Conclusion The genetic variation of ELL2 may play an important role in the occurrence of pleomorphic adenoma of salivary gland,and smoking combined with the 1119C allele increased the risk of this disease.