Laboratory of molecular genetics and immunology, Department of Pathological Science, Londrina State University, Londrina, PR, Brazil.
Laboratory of study and application of DNA polymorphism, Department of Pathological Science, Londrina State University, Londrina, PR, Brazil.
J Biomed Sci. 2018 Sep 18;25(1):69. doi: 10.1186/s12929-018-0472-y.
Human papillomavirus (HPV) is the most common sexually transmitted virus in women worldwide. The persistence of the virus may cause warts that are considered benign lesions and low or high grade intraepithelial lesions (LSIL/HSIL). Immunological system plays an important role in the resolution of infections. In this context, we highlight the chemokines, which are important regulators in the development of viral infections and inflammation. Among which CXCL12 stands out, due to its pro-inflammatory features, acting as chemoattractant recruiting immune cells. Several polymorphisms were identified in CXCL12 gene including rs1801157 in the 3'-untranslated region, which is characterized by a substitution of a guanine for an adenine.
In this study, 195 women were classified as HPV non-infected and 169 as HPV-infected. HPV-DNA was detected by polymerase chain reaction (PCR) and the polymorphism was assessed in blood cells through restriction fragment length polymorphism analysis.
HPV infection was more incident in women who had more than 4 sexual partners during lifetime (p = 0.007), among those who presented lower number of pregnancies (p = 0.017). HPV was more prevalent among allele A carriers confirmed by logistic regression analysis adjusted for several confounding factors [OR = 4.985; CI (2.85-8.72), p < 0.001]. An association between allele A carriers and HSIL development (p = 0.003) was also observed.
In the present study, we demonstrated that CXCL12 rs1801157 is independently associated with HPV infection and exerts influence in HSIL development, suggesting it as a promising susceptibility biomarker for HPV infection and lesions development.
人乳头瘤病毒（HPV）是全球女性中最常见的性传播病毒。病毒的持续存在可能导致被认为是良性病变的疣以及低级别或高级别上皮内病变（LSIL/HSIL）。免疫系统在感染的解决中起着重要作用。在这种情况下，我们强调趋化因子，它们是病毒感染和炎症发展的重要调节剂。其中 CXCL12 最为突出，因为它具有促炎特征，作为趋化因子招募免疫细胞。CXCL12 基因中已经鉴定出几种多态性，包括 3'非翻译区的 rs1801157，其特征是腺嘌呤被鸟嘌呤取代。
在这项研究中，195 名女性被归类为 HPV 未感染，169 名女性被归类为 HPV 感染。通过聚合酶链反应（PCR）检测 HPV-DNA，通过限制性片段长度多态性分析评估血液细胞中的多态性。
HPV 感染在一生中性伴侣超过 4 个的女性中更为常见（p=0.007），在妊娠次数较少的女性中更为常见（p=0.017）。通过调整多种混杂因素的逻辑回归分析，证实等位基因 A 携带者的 HPV 感染更为普遍[OR=4.985；95%CI（2.85-8.72），p<0.001]。还观察到等位基因 A 携带者与 HSIL 发展之间存在关联（p=0.003）。
在本研究中，我们证明 CXCL12 rs1801157 与 HPV 感染独立相关，并对 HSIL 发展产生影响，表明其作为 HPV 感染和病变发展的有前途的易感性生物标志物。
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