Dirección de Infecciones Crónicas y Cáncer, Centro de Investigación sobre Enfermedades Infecciosas (CISEI), Instituto Nacional de Salud Pública, Av, Universidad 655, Santa María Ahuacatitlán, Cuernavaca, C,P,62100, Cuernavaca, México.
Infect Agent Cancer. 2012 Nov 14;7(1):32. doi: 10.1186/1750-9378-7-32.
Women with Human Papilloma Virus (HPV) persistence are characterized by high levels of IL-10 at cervix. We have determined whether polymorphisms of IL-10 gene promoter might be associated with increased risk of squamous intraepithelial cervical lesions (SICL) and whether exist significative differences of IL-10 mRNA expression at cervix and systemic and serum IL-10 protein between SICL cases and non-Cervical Lesions (NCL).
Peripheral blood samples from SICL (n = 204) and NCL (n = 166) were used to detect IL-10 promoter polymorphisms at loci -592A/C (rs1800872), -819C/T (rs1800871), -1082A/G (rs1800896), -1352A/G (rs1800893), by allelic discrimination and to evaluate serum IL-10 protein. Cervical epithelial scrapings from NCL and biopsies from SICLs were used for HPV-typing and to evaluate IL-10 mRNA expression level. The systemic and local IL-10 mRNA expression levels were measured by real time-PCR. Genotypic and allelic frequencies of the selected polymorphisms were analyzed by logistic regression, adjusting by age and HPV-genotype, to determine the association with SICL.
No significant differences were found between genotype frequencies at loci -819, -1082, and -1352. Individuals carrying at least one copy of risk allele A of polymorphism -592 had a two-fold increased risk of developing SICL [adjusted odds ratio (OR), 2.02 (95% CI, 1.26-3.25), p = 0.003], compared to NCL. The IL-10 mRNA expression and serum IL-10 protein, were significantly higher in SICL cases (p < 0.01), being higher in patients carrying the risk allele A.
The -592 polymorphism is associated with increased risk of SICL and can serve as a marker of genetic susceptibility to SICL among Mexican women. According to IL-10 levels found in SICL, IL-10 can be relevant factor for viral persistence and progression disease.
HPV 持续感染的女性在宫颈部位表现出高水平的 IL-10。我们已经确定 IL-10 基因启动子的多态性是否与鳞状上皮内宫颈病变 (SICL) 的风险增加有关，以及 SICL 病例与非宫颈病变 (NCL) 之间宫颈、系统和血清 IL-10 蛋白的 IL-10 mRNA 表达是否存在显著差异。
使用来自 SICL（n=204）和 NCL（n=166）的外周血样本，通过等位基因鉴别法检测 IL-10 启动子 -592A/C（rs1800872）、-819C/T（rs1800871）、-1082A/G（rs1800896）、-1352A/G（rs1800893）的多态性，并评估血清 IL-10 蛋白。使用 HPV 分型和实时 PCR 评估来自 NCL 的宫颈上皮刮片和来自 SICL 的活检的 IL-10 mRNA 表达水平。使用实时 PCR 测量系统和局部的 IL-10 mRNA 表达水平。通过逻辑回归分析，调整年龄和 HPV 基因型，对所选多态性的基因型和等位基因频率进行分析，以确定与 SICL 的相关性。
在 -819、-1082 和 -1352 位点的基因型频率无显著差异。与 NCL 相比，携带 -592 多态性风险等位基因 A 的个体患 SICL 的风险增加了两倍 [校正比值比 (OR)，2.02（95%CI，1.26-3.25），p=0.003]。SICL 病例的 IL-10 mRNA 表达和血清 IL-10 蛋白显著升高（p<0.01），携带风险等位基因 A 的患者升高更为明显。
-592 多态性与 SICL 的风险增加相关，可作为墨西哥女性 SICL 遗传易感性的标志物。根据在 SICL 中发现的 IL-10 水平，IL-10 可能是病毒持续存在和疾病进展的相关因素。
