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中国南方人群中HLA-DRB1基因多态性、高危型人乳头瘤病毒感染与宫颈病变的相关性

Association between HLA-DRB1 polymorphism, high-risk HPV infection and cervical neoplasia in southern Chinese.

作者信息

Chan Paul K S, Cheung Tak-Hong, Lin C K, Siu Shing-Shun N, Yim So-Fan, Lo Keith W K, Cheung Jo L K, Tam Ann O Y, Tang Julian W

机构信息

Department of Microbiology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong Special Administrative Region, Hong Kong, China.

出版信息

J Med Virol. 2007 Jul;79(7):970-6. doi: 10.1002/jmv.20805.

Abstract

Multiple determinants are involved in the progression of human papillomavirus (HPV)-infected cervical lesion to invasive cancer. Human leukocyte antigen (HLA) polymorphism seems to play a role. This study examined the association between HLA-DRB1 polymorphism, high-risk HPV infection, and the development of cervical neoplasia in southern Chinese. Three hundred and seventy women with cervical neoplasia (43 cervical intraepithelial neoplasia grade II, 154 grade III, and 173 invasive cancers) and 323 controls were recruited for HLA-DRB1 typing by a sequence-based approach. Cervical specimens were collected for HPV detection by a consensus primer-based polymerase chain reaction, and with the type of HPV identified by hybridization with type-specific oligonucleotide probes. A protective effect of HLA-DRB112 for cervical neoplasia was observed, and with stronger associations when subgroup analyses were carried out for patients infected with HPV16 and HPV58. The protective effect of HLA-DRB113 that had been reported from other populations was not observed. The data obtained in this study showed that HLA-DRB1*03 conferred a higher risk for HPV18-infected, but not for HPV16-, HPV52-, or HPV58-infected cervical lesions. Although, HPV52 was reported as uncommon worldwide, it was found to be the second most prevalent type in the southern Chinese population. However, no additional risk association was observed when subgroup analyses were performed for HPV52-infected patients. The current study shows that, among southern Chinese, the outcome of HPV-infected cervical lesions is associated with HLA-DRB1 polymorphism. These associations often vary with the type of HPV infection.

摘要

多种决定因素参与了人乳头瘤病毒(HPV)感染的宫颈病变发展为浸润性癌的过程。人类白细胞抗原(HLA)多态性似乎发挥了作用。本研究调查了中国南方人群中HLA-DRB1多态性、高危HPV感染与宫颈肿瘤发生之间的关联。采用基于序列的方法,招募了370例宫颈肿瘤患者(43例宫颈上皮内瘤变II级、154例III级和173例浸润性癌)和323例对照进行HLA-DRB1分型。采集宫颈标本,通过基于共识引物的聚合酶链反应检测HPV,并通过与型特异性寡核苷酸探针杂交鉴定HPV类型。观察到HLA-DRB112对宫颈肿瘤具有保护作用,对感染HPV16和HPV58的患者进行亚组分析时,关联更强。未观察到其他人群中报道的HLA-DRB113的保护作用。本研究获得的数据表明,HLA-DRB1*03使感染HPV18的宫颈病变风险更高,但对感染HPV16、HPV52或HPV58的宫颈病变无此作用。尽管HPV52在全球范围内报道较少,但在中国南方人群中它是第二常见的类型。然而,对感染HPV52的患者进行亚组分析时,未观察到其他额外的风险关联。当前研究表明,在中国南方人群中,HPV感染的宫颈病变结局与HLA-DRB1多态性相关。这些关联通常因HPV感染类型而异。

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