Frequency of interleukin-4 (IL-4)-589 gene polymorphism and vaginal concentrations of IL-4, nitric oxide, and mannose-binding lectin in women with recurrent vulvovaginal candidiasis
Frequency of interleukin-4 (IL-4)-589 gene polymorphism and vaginal concentrations of IL-4, nitric oxide, and mannose-binding lectin in women with recurrent vulvovaginal candidiasis
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DOI：
10.1086/429246
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发表时间：
2005-05-01
影响因子：
11.8
通讯作者：
Witkin, SS
中科院分区：
文献类型：
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作者：
Babula, O;Lazdane, G;Witkin, SS
背景在白细胞介素-4（IL-4）基因中位置-589处的C -> T取代与IL-4的产生增加相关。该多态性与复发性外阴阴道念珠菌病（RVVC）以及阴道IL-4、抗念珠菌化合物一氧化氮（NO）和甘露糖结合凝集素（MBL）浓度之间的关系进行了评估。采用酶联免疫吸附试验检测42例RVVC急性期患者和43例对照组患者阴道灌洗液中IL-4和NO代谢产物的含量。采用聚合酶链反应-酶切法检测IL-4基因-589位点多态性。采用Fisher精确检验、非参数Mann-Whitney检验和Kruskal-Wallis检验分析数据，认为斯皮尔曼等级相关P <0.05具有显著性。在38例RVVC患者中鉴定出白色念珠菌;另外3例因热带念珠菌感染，1例因克柔念珠菌感染。RVVC组IL-4 T、T基因型检出率为59.5%，对照组为7.0%（P <0.001）。RVVC组IL-4*T阳性率为76.2%，对照组为23.3%（P <0.0001）。与对照组相比，RVVC患者阴道IL-4的中位浓度升高（P <0.0001）。相反，RVVC患者的NO代谢物（P = 0.02）和MBL（P <0.0001）的阴道浓度降低。IL- 4*T纯合性与阴道IL-4水平呈正相关（P < .0001），与阴道NO（P = .01）和MBL（P < .0001）浓度呈负相关。在IL-4*T纯合子中，阴道抗Candidal因子水平降低可能增加RVVC的易感性。
Background. A C -> T substitution at position -589 in the interleukin-4 (IL-4) gene is associated with increased production of IL-4. Associations between this polymorphism and recurrent vulvovaginal candidiasis (RVVC), as well as vaginal concentrations of IL-4 and the anticandidal compounds nitric oxide ( NO) and mannose binding lectin (MBL), were evaluated.Methods. Vaginal samples obtained by lavage from 42 women with RVVC during the acute stage of the disease and 43 control samples were assayed by enzyme-linked immunosorbent assay for IL-4 and NO metabolites. The -589 IL-4 gene polymorphism was detected by polymerase chain reaction and endonuclease digestion. Data were analyzed by Fisher's exact test, the nonparametric Mann-Whitney and Kruskal-Wallis tests, and Spearman rank correlation P < .05 was considered significant.Results. Candida albicans was identified in 38 patients with RVVC; 3 others had infection due to Candida tropicalis, and 1 had infection due to Candida krusei. The IL-4 T, T genotype was detected in 59.5% of patients with RVVC and in 7.0% of control subjects (P < .001). The frequency of IL-4*T was 76.2% in patients with RVVC and 23.3% in control subjects (P < .0001). The median concentration of vaginal IL-4 was elevated in patients with RVVC, compared with control subjects (P < .0001). Conversely, vaginal concentrations of NO metabolites (P = .02) and MBL (P < .0001) were reduced in patients with RVVC. There was a positive association between IL- 4*T homozygosity and vaginal IL-4 levels (P < .0001) and negative associations between this genotype and vaginal NO (P = .01) and MBL (P < .0001) concentrations.Conclusions. Reduced vaginal levels of anticandidal factors in IL-4*T homozygotes may increase susceptibility to RVVC.