年轻宫颈癌患者人类白细胞抗原-DRB1与-DQB1基因多态性及与人乳头瘤病毒16感染的关系

Polymorphism of HLA-DRB1 and -DQB1 alleles among young women with cervical squamous cell carcinoma and its relation with human papillomavirus type 16 infection

目的 分析年轻妇女宫颈癌人类白细胞抗原（HLA）-DRB1与-DQBI等位基因的多态性分布及与人乳头瘤病毒（HPV）16亚型感染的关系.方法 选择温州医学院附属第一医院妇产科2005年1月至2009年8月诊治的166例宫颈鳞状上皮癌患者,分为低龄组（年龄≤35岁,59例）,高龄组（107例）.以同期因子宫肌瘤收治患者共50例为正常对照组.采用聚合酶链反应检测宫颈组织中HPV16感染情况,同时采用多聚酶链反应-序列特异性引物方法检测患者HLA-DRB1与-DRQ1等位基因,计算等位基因频率.结果 （1）HLA-DQB1＊0301亚型基因频率在HPV16阳性的低龄宫颈癌患者中为29.6%,高龄组为12.9%,差异有统计学意义（P〈0.05）.HLA-DRB1＊04、-DRB1＊09亚型的基因频率在HPV16阴性的低龄宫颈癌患者中分别为14.1%与26.6%,高龄组为5.9%与10.5%,差异有统计学意义（P〈0.05）.HLA-DRB1＊07亚型在HPV16阴性的低龄宫颈癌患者中未检出,而在高龄组检出14例（9.2%）,差异有统计学意义（P〈0.05）.（2）低龄宫颈癌组HLA-DQB1＊0501亚型的基因频率在HPV16阳性与阴性患者中分别为7.4%与6.3%,均明显低于高龄组的25.8%与20.4%,差异有统计学意义（P〈0.05）.结论 年轻宫颈癌患者某些HLA-DRB1、-DQB1等位基因亚型分布不同于年长者,并且与其HPV16感染状态存在一定关系.

Objective To investigate the polymorphism of human leukocyte antigen （HLA）-DRB1 and-DQB1 alleles among young women with cervical squamous cell carcinoma （SCC） and elucidate its relationship with human papillomavirus （HPV） type 16 infection.Methods From January 2005 to August 2009,166 women diagnosed with cervical SCC at our hospital were enrolled.Thsse patients were divided into two groups based on age,including 59 cases in young age group （ ≤35 yrs） and 107 cases in non-young age group.In the mean time,50 cases with uterine myoma treated by hysterectomy were selected as controls.HPV 16 DNA in cervical tissues was amplified by polymerase chain reaction （PCR）.HLA-DRB1 and -DQB1 typing were carried out by PCR-sequence specific primer （PCR-SSP） and the allele frequencies calculated.Results （1）The allele frequency of HLA DQB1 ＊ 0301 at 29.6% was detected among HPV 16positive cervical SCC cases in young age group.And it was significantly higher than 12.9% of non-young age group （P〈0.05 ）.The allele frequencies of HLA-DRB1 ＊ 04 and -DRB1 ＊ 09 were significantly higher among HPV 16 negative cervical SCC cases in young age group as compared with non-young age group （14.1%,26.6% vs 5.9%,10.5%） （P〈0.05）.The HLA-DRB1 ＊07 allele was not detected among HPV 16 negative cervical SCC cases in young age group,But 14 cases （9.2%） were detected in non-young age group （P〈0.05）.（2）The allele frequencies of HLA-DQB1 ＊ 0501 at 7.4% and 6.3% respectively were detected among HPV 16 positive and negative cervical SCC cases in the young age group.And they were significantly lower than 25.8% and 20.4% of non-young age group （ P〈0.05 ）.Conclusion The distribution patterns of HLA-DRB1 and -DQB1 alleles among young women with cervical SCC are different from those of older ones.And it has something to do with the HPV 16 infection status.