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白细胞介素-13 rs1800925/-1112C/T 启动子单核苷酸多态性变异与津巴布韦穆雷瓦区成年男性抗血吸虫病有关。

Interleukin-13 rs1800925/-1112C/T promoter single nucleotide polymorphism variant linked to anti-schistosomiasis in adult males in Murehwa District, Zimbabwe.

机构信息

School of Public Health Medicine, College of Health Sciences, University of KwaZulu-Natal, Durban, South Africa.

School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa.

出版信息

PLoS One. 2021 May 28;16(5):e0252220. doi: 10.1371/journal.pone.0252220. eCollection 2021.

DOI:10.1371/journal.pone.0252220
PMID:34048465
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8162643/
Abstract

BACKGROUND

Chronic schistosomiasis is predominantly induced through up-regulation of inflammatory cytokines such as interleukin (IL)-13. IL-13 may contribute to the disease outcomes by increasing eosinophil infiltration thereby promoting fibrosis. IL-13 may act as an immunosuppressive inflammatory cytokine that may promote carcinogenesis and also may offer protection against schistosomiasis thereby reducing risk of schistosome infections. Our study evaluated the frequency of the IL-13 rs1800925/-1112 C/ T promoter single nucleotide polymorphisms (SNPs) among schistosomiasis infected individuals and assessed the association of the variants on IL-13 cytokine levels. We also investigated IL-13 rs1800925 polymorphisms on prostate-specific antigen levels as an indicator for risk of prostate cancer development.

METHODOLOGY

The study was cross-sectional and included 50 schistosomiasis infected and 316 uninfected male participants residing in Murehwa District, Zimbabwe. IL-13 rs1800925 SNPs were genotyped by allele amplification refractory mutation system-polymerase chain reaction. Concentrations of serum prostate-specific antigens and plasma IL-13 were measured using enzyme-linked immunosorbent assay.

RESULTS

Frequencies of the genotypes CC, CT and TT, were 20%, 58% and 22% in schistosomiasis infected, and 18.3%, 62.1% and 19.6% in uninfected participants with no statistical differences. There were significantly (p<0.05) higher IL-13 cytokine levels among both infected and uninfected participants with the genotypes CC and CT; median 92.25 pg/mL and 106.5 pg/mL, respectively, compared to TT variant individuals; 44.78 pg/mL. Within the schistosomiasis uninfected group, CC and CT variants had significantly (p<0.05) higher IL-13 levels; median 135.0 pg/mL and 113.6 pg/mL, respectively compared to TT variant individuals; 47.15 pg/mL. Within the schistosomiasis infected group, CC, CT and TT variant individuals had insignificant differences of IL-13 level. Using logistic regression, no association was observed between prostate-specific antigen levels, IL-13 cytokine levels and IL-13 rs1800925 variants (p>0.05).

CONCLUSION

IL-13 rs1800925 C variant individuals had the highest IL-13 cytokine levels among the schistosomiasis uninfected suggesting that they may be protective against Schistosoma infections. There was no association between IL-13 concentrations or IL-13 rs1800925 variants and risk of prostate cancer indicating that IL-13 levels and IL-13 rs10800925 may not be utilised as biomarker for risk of prostate cancer in schistosome infections.

摘要

背景

慢性血吸虫病主要是通过白细胞介素 (IL)-13 等炎症细胞因子的上调引起的。IL-13 可能通过增加嗜酸性粒细胞浸润从而促进纤维化来导致疾病结局。IL-13 可能作为一种免疫抑制性炎症细胞因子,促进致癌作用,并可能对血吸虫病提供保护,从而降低血吸虫感染的风险。我们的研究评估了血吸虫病感染者中白细胞介素 (IL)-13 rs1800925/-1112 C/T 启动子单核苷酸多态性 (SNP) 的频率,并评估了变体对白细胞介素 13 细胞因子水平的影响。我们还研究了白细胞介素 13 rs1800925 多态性对前列腺特异性抗原水平的影响,作为前列腺癌发展风险的指标。

方法

本研究为横断面研究,纳入了津巴布韦穆雷瓦区 50 名血吸虫病感染者和 316 名未感染者。通过等位基因扩增抑制突变系统-聚合酶链反应对白细胞介素 13 rs1800925SNP 进行基因分型。采用酶联免疫吸附试验测量血清前列腺特异性抗原和血浆白细胞介素 13 的浓度。

结果

在血吸虫病感染者中,基因型 CC、CT 和 TT 的频率分别为 20%、58%和 22%,在未感染者中分别为 18.3%、62.1%和 19.6%,无统计学差异。感染和未感染参与者的基因型 CC 和 CT 白细胞介素 13 细胞因子水平显著升高(p<0.05);分别为 92.25pg/mL 和 106.5pg/mL,而 TT 变体个体为 44.78pg/mL。在未感染血吸虫病的人群中,CC 和 CT 变体的白细胞介素 13 水平显著升高(p<0.05);分别为 135.0pg/mL 和 113.6pg/mL,而 TT 变体个体为 47.15pg/mL。在感染血吸虫病的人群中,CC、CT 和 TT 变体个体的白细胞介素 13 水平无显著差异。使用逻辑回归,未发现前列腺特异性抗原水平、白细胞介素 13 细胞因子水平和白细胞介素 13 rs1800925 变体之间存在关联(p>0.05)。

结论

未感染血吸虫病的人群中,白细胞介素 13 rs1800925C 变体个体的白细胞介素 13 细胞因子水平最高,表明他们可能对血吸虫感染具有保护作用。白细胞介素 13 浓度或白细胞介素 13 rs1800925 变体与前列腺癌风险之间无关联,表明白细胞介素 13 水平和白细胞介素 13 rs10800925 可能不能作为血吸虫感染中前列腺癌风险的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78ba/8162643/50b187d639bb/pone.0252220.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78ba/8162643/abdb70b021af/pone.0252220.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78ba/8162643/33e613397bf7/pone.0252220.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78ba/8162643/82e8f4841288/pone.0252220.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78ba/8162643/68cbc48b374c/pone.0252220.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78ba/8162643/50b187d639bb/pone.0252220.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78ba/8162643/abdb70b021af/pone.0252220.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78ba/8162643/33e613397bf7/pone.0252220.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78ba/8162643/82e8f4841288/pone.0252220.g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78ba/8162643/50b187d639bb/pone.0252220.g005.jpg

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