Berti Fernanda Costa Brandão, Pereira Ana Paula Lombardi, Trugilo Kleber Paiva, Cebinelli Guilherme Cesar Martelossi, Silva Lorena Flor da Rosa Santos, Lozovoy Marcell Alysson Batisti, Simão Andréa Name Colado, Watanabe Maria Angelica Ehara, de Oliveira Karen Brajão
Department of Pathological Sciences, Biological Sciences Center, Londrina State University, Londrina, Parana, Brazil.
Department of Clinical Pathology, Clinical Analysis and Toxicology, Health Sciences Center, Londrina State University, Londrina, Parana, Brazil.
Infect Genet Evol. 2017 Sep;53:128-134. doi: 10.1016/j.meegid.2017.05.020. Epub 2017 May 25.
Interleukin-10 (IL-10) influences HPV infection and viral persistence, favoring cervical immunosuppression and cervical carcinogenesis. IL-10 levels may be influenced by HPV itself and by IL-10 polymorphisms, including rs1800872 (c.-592C>A). Therefore, we evaluated the influence of IL-10 c.-592C>A polymorphism in HPV infection and in IL-10 plasmatic/cervical levels in HPV infected and non-infected women. The study included 174 infected and 186 non-infected patients. Cervical epithelial scrapings were obtained to determine HPV DNA presence PCR. Peripheral blood samples were obtained to determine IL-10 polymorphism by PCR-RFLP, while IL-10 levels were assessed by ELISA. HPV was more prevalent among allele A carriers (p<0.001), with IL-10 c.-592C>A polymorphism being associated with HPV infection. As demonstrated by binary logistic regression analysis, heterozygotes [OR=2.081 95% CI (1.222-3.544), p=0.007] and homozygotes [OR=3.745 95% CI (1.695-8.271), p=0.001] showed approximately 2 and 4 time's greater odds, respectively, of presenting HPV when compared to CC patients. Moreover, HPV infected patients carrying polymorphic allele A showed higher IL-10 cervical levels (p=0.039). Binary logistic regression analysis demonstrated that IL-10 cervical levels were not independently associated to CA+AA genotypes (p=0.162), neither to HPV's presence (p=0.061), thus IL-10 cervical levels are possibly increased because of both HPV and allele A presence. Taken together, these findings suggest that IL-10 c.-592C>A polymorphism is independently associated with HPV infection susceptibility exerting influence on IL-10 cervical levels in HPV infected women, thus contributing to cervical carcinogenesis.
白细胞介素-10（IL-10）影响人乳头瘤病毒（HPV）感染及病毒持续存在，促进宫颈免疫抑制和宫颈癌发生。IL-10水平可能受HPV自身及IL-10基因多态性影响，包括rs1800872（c.-592C>A）。因此，我们评估了IL-10 c.-592C>A基因多态性对HPV感染以及HPV感染和未感染女性IL-10血浆/宫颈水平的影响。该研究纳入了174例感染患者和186例未感染患者。采集宫颈上皮刮片，通过PCR检测HPV DNA的存在情况。采集外周血样本，通过PCR-RFLP检测IL-10基因多态性，同时采用ELISA法评估IL-10水平。等位基因A携带者中HPV更为常见（p<0.001），IL-10 c.-592C>A基因多态性与HPV感染相关。二元逻辑回归分析显示，与CC基因型患者相比，杂合子[比值比（OR）=2.081，95%置信区间（CI）（1.222 - 3.544），p=0.007]和纯合子[OR=3.745，95%CI（1.695 - 8.271），p=0.001]出现HPV的几率分别高出约2倍和4倍。此外，携带多态性等位基因A的HPV感染患者宫颈IL-10水平较高（p=0.039）。二元逻辑回归分析表明，宫颈IL-10水平与CA + AA基因型（p=0.162）以及HPV的存在（p=0.061）均无独立相关性，因此宫颈IL-10水平可能因HPV和等位基因A的共同存在而升高。综上所述，这些发现表明IL-10 c.-592C>A基因多态性与HPV感染易感性独立相关，对HPV感染女性的宫颈IL-10水平产生影响，从而促进宫颈癌发生。
