p73第2外显子第4和14位基因多态性与人乳头状瘤病毒易感性的相关性研究

Correlation between polymorphisms at position 4 and 14 in exon 2 of the p73 gene and susceptibility to human papillomavirus infection

目的探讨人乳头状瘤病毒（HPV）易感性与p73基因第2外显子第4和14位碱基多态性的相关性。方法收集南京地区尖锐湿疣患者83例、Bowen样丘疹病患者11例的皮损和血样，以在性病门诊进行健康体检的性病高危人群150例为阴性对照，采用直接测序法检测皮损中感染的HPV—DNA序列，并在GenbankBlast上进行比对，鉴定HPV型别，抽提尖锐湿疣和Bowen样丘疹病患者以及阴性对照组的血样DNA，以shP73引物对p73基因片段进行扩增和测序，检测患者和阴性对照组的p73第2外显子第4和14位基因的多态性，分析HPV易感性和宿主p73基因多态性之间的相关性。结果83例尖锐湿疣患者皮损中HPV-6型35例占42．2％，HPV-11型34例占41．0％；11例Bowen样丘疹病患者皮损中HPV-16型5例（5／11），HPV-6型3例（3／11）。p73基因多态性检测，83例尖锐湿疣患者血样测序阳性83例，11例Bowen样丘疹病患者血样测序阳性11例，对照组150例血样测序阳性132例。与对照组相比，三种基因型中，A4T14／A4T14基因型感染HPV患尖锐湿疣（OR=4．89，95％C／=1．50～15．91）或Bowen样丘疹病（OR=7．11，95％CI=1．144—44．20）的风险更高。G4C14／G4C14基因型与其他两种基因型相比，感染HPV后患Bowen样丘疹病的风险较低（OR=0．16，95％CI=0．04～0．65）。结论p73第2外显子携带A4T14基因增加了Bowen样丘疹病和尖锐湿疣的患病风险，但其第4和14位碱基的多态性与罹患高危型与低危型HPV之间并无明显的相关性。

Objective To analyze the correlation between polymorphisms at position 4 and 14 in exon 2 of the p73 gene and susceptibility to human papillomavirus （HPV） infection. Methods Tissue specimens were obtained from the lesions of 83 patients with condyloma acuminatum and 11 patients with bowenoid papulosis, and blood samples from all the patients as well as 150 health checkup examinees with high risk for sexually transmitted diseases （STDs） at STD clinics （negative control group）. PCR was performed to detect HPV DNA in lesional tissue specimens, followed by direct sequencing and nucleotide alignment using the BLAST program for the determination of HPV genotypes. To assess polymorphisms at position 4 and 14 in exon 2 of the p73 gene, DNA was extracted from all the blood samples, and the p73 gene was amplified by PCR with the primer shP73 followed by gene sequencing. The association between the polymorphisms and susceptibility to HPV infection was analyzed. Results Of the 83 tissue specimens from patients with condyloma acuminatum, 42.2% （35/83） were positive for HPV 6, and 41.0% （34/83） for HPV 11. Among the 11 tisssue specimens from bowenoid papulosis lesions, 5 were positive for HPV 16, and 3 for HPV 6. The p73 gene was successfully amplified and sequenced from all the patients with condyloma acuminatum or bowenoid papulosis as well as from 132 out of 150 health checkup examinees. There were three genotypes at position 4 and 14 in exon 2 of the p73 gene, including A4T14/G4C14, A4T14/A4T14, G4C14/G4C14, of which, A4T14/A4T14 was associated with a higher risk for condyloma acuminatum （OR 4.89, 95% CI 1.50 - 15.91 ） as well as bowenoid papulosis （OR 7.11, 95% CI 1.144 - 44.20）, and G4C14/G4C14 with a lower risk for bowenoid papulosis （OR 0.16, 95% CI0.04 - 0.65）, in patients with HPV infection. Conclusions The A4T14 allele in exon 2 of the p73 gene increases the risk for bowenoid papulosis and condyloma acuminatum, but no significant correlation is found between the susceptibility to high- or low-risk HPV infection and polymorphisms at the two positions in the p73 gene.