VDR基因多态性与宫颈病变及HPV感染转归的相关性

Correlation of vitamin D receptor gene polymorphisms with cervical lesions and regression of HPV infection

目的 分析维生素D受体(vitamin D receptor, VDR)基因多态性与宫颈病变的关系,并探讨其对高危型人乳头瘤病毒(high risk-human papillomavirus, HR-HPV)感染转归的影响。方法 选取2020年9月至2021年10月于山西医科大学第二医院行阴道镜检查的患者376例,将病理结果示慢性宫颈炎和宫颈上皮内瘤变Ⅰ级者设为对照组(188例),宫颈上皮内瘤变Ⅱ级及以上者(CINⅡ+)为病例组(188例)。收集患者外周静脉血行VDR基因多态性检测,包括FOKI、BsmL、Apal和Taql的单核苷酸多态性(single nucleotide polymorphisms, SNPs)位点,分析VDR基因多态性与宫颈病变的关系。对选择行宫颈锥形切除术进行治疗的142例CINⅡ-Ⅲ级患者的HPV转归情况进行6个月的随访,根据随访结果分为HPV转阴者和同一型别HPV持续感染者,即转阴组和持续感染组,分析VDR基因多态性是否影响HPV感染的转归。结果 随访结果显示,104例患者的HPV感染呈转阴状态,33例患者持续感染同一型别的HPV,而另外5例患者则感染了其他型别的HPV。VDR基因多态性检测结果表明,FOKI SNPs ff基因型及f等位基因与CINⅡ+发生显著相关(P<0.05),并且与HR-HPV持续感染相关(P<0.05);TaqI SNPs tt及Tt基因型均增加CINⅡ+发生的风险(P<0.05),t等位基因与CINⅡ+发生风险增加有关(P<0.05),但与HPV持续感染未见相关性(P>0.05)。结论 VDR基因多态性与宫颈病变及HR-HPV感染转归相关,其中FOKI SNPs ff基因型及f等位基因和TaqI SNPs tt、Tt基因型及t等位基因与宫颈病变的发生存在关联,并且FOKI SNPs ff基因型及f等位基因可能影响HR-HPV感染的转归结果。

Objective To analyze the relationship between vitamin D receptor(VDR)gene polymorphisms and cervical lesions,and explore VDR gene polymorphism on the progression of high-risk human papillomavirus(HR-HPV)infection.Methods A total of 376 patients who underwent colposcopy in the Second Hospital of Shanxi Medical University from September 2020 to October 2021 were selected.According to pathological results,the patients were divided into control group(188 cases of chronic cervicitis and CINⅠ)and case group(188 cases of CINⅡor above).Peripheral venous blood samples from the 376 patients were collected for VDR gene polymorphisms,including four single nucleotide polymorphisms(SNPs)sites:FOKI,BsmI,ApaI,and TaqI,and the relationships between VDR gene polymorphisms and cervical lesions were analyzed.Among the 142 patients who underwent cervical conization for CINⅡ-Ⅲ,the outcomes of HR-HPV infection were followed up for 6 months.Based on the follow-up results,the patients were divided into two groups:clearance group(HPV negative)and persistent infection group(persistent infection with the same HPV type),and the impact of VDR gene polymorphisms on the outcome of HPV infection was analyzed.Results The follow-up results showed that HPV infection became negative in 104 patients,33 patients continued to be infected with the same type of HPV,and 5 patients were infected with other types of HPV.The FOKI SNPs ff genotype and f allele were significantly associated with the occurrence of CINⅡ+(P<0.05),and also related to persistent high-risk human papillomavirus(HR-HPV)infection(P<0.05).The TaqI SNPs tt and Tt genotypes increased the risk of CINⅡ+occurrence(P<0.05),and the t allele was associated with an increased risk of CINⅡ+(P<0.05),but not with persistent HPV infection(P>0.05).Conclusion VDR gene polymorphisms are associated with cervical lesions and the outcome of HR-HPV infection.Specifically,the FOKI SNPs ff genotype and f allele,and the TaqI SNPs tt and Tt genotypes and t allele are associated to the occurrence of cervical lesions.Furthermore,the FOKI SNPs ff genotype and f allele may influence the outcome of HR-HPV infection.