TNF-β和IFN-α基因多态性与HPV感染预后的关系研究

Study on the correlation between TNF-βand IFN-αgene polymorphism and the prognosis of HPV infection

目的探讨肿瘤坏死因子-β(TNF-β)和干扰素-α(IFN-α)基因多态性与HPV感染预后的相关性,探索TNF-β、IFN-α基因在HPV感染相关宫颈病变发生及进展中可能起到的作用。方法收集本院2018年1月~2019年6月高危型HPV阳性病例共236例,根据病理确诊CIN级别分为病理正常组、CINⅠ组、CINⅡ组、CINⅢ组以及宫颈癌组,每组分别45、48、47、50、46例,同时以体检HPV和病理细胞学检测均阴性人员共56份样本作为对照。运用PCR扩增和Sanger测序法检测不同组别TNF-β的候选SNP rs909253、rs2239704和IFN-α的候选SNP rs6475526 SNP位点,统计和分析SNP等位基因频率。结果CINⅠ组、CINⅡ组、CINⅢ组以及宫颈癌组、病理正常组及对照组比较发现:rs909253、rs2239704、rs6475526基因型分布频率和等位基因分布频率存在明显差异。CC基因型携带者的HPV感染的累积阴性率最低,且该型携带者的预后更差,复发率更高,更容易在高级宫颈疾病组出现。结论建立TNF-β的候选SNP rs909253、rs2239704和IFN-α的候选SNP rs6475526的PCR基因扩增+Sanger(第一代)测序检测方法,能够准确识别并判读SNP的类型,构建分子分型模型,用于判断患者预后恢复情况,对临床做出正确的评估。

Objective To explore the correlation between the genes polymorphism of tumor necrosis factor-β(TNF-β)and interferon-α(IFN-α)and the prognosis of human papillomavirus(HPV)infection,and to explore the possible role of TNF-βand IFN-αgenes in occurrence and progression of HPV-infection related cervical lesions.Methods A total of 236 high-risk HPV positive patients from January 2018 to June 2019 in our hospital were collected and divided into the normal pathological group,the CINⅠgroup,the CINⅡgroup,the CINⅢgroup and cervical cancer group according to the CIN grade confirmed by pathology,with 45,48,47,50,46 cases in each group respectively.A total of 56 samples with negative HPV and pathological cytology were used as controls.Polymerase chain reaction(PCR)amplification and Sanger sequencing were used to detect the TNF-βcandidate SNP rs909253,rs2239704 and IFN-αcandidate SNP rs6475526 SNP loci in different groups,and the SNP allele frequency was statistically analyzed.Results The comparison between CINⅠgroup,CINⅡgroup,CINⅢgroup,cervical cancer group,pathologically normal group and control group showed that there were significant differences in the distribution frequencies of genotypes and alleles of rs909253,rs2239704,and rs6475526.Carriers of CC genotype had the lowest cumulative negative rate of HPV infection,the prognosis of this type of carrier was worse,the recurrence rate was higher,and it was more likely to appear in the advanced cervical disease group.Conclusion The establishment of PCR gene amplification+Sanger(generationⅠ)sequencing detection method for TNF-βcandidate SNP rs909253,rs2239704 and IFN-αcandidate SNP rs6475526 can accurately identify and interpret the type of SNP and construct molecular typing model that can be used to judge the prognosis of the patient and make a correct assessment in clinic.