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白细胞介素-10 启动子变异在尼日利亚儿童疟疾和血吸虫病单感染及混合感染中的差异贡献。

Differential contribution of interleukin-10 promoter variants in malaria and schistosomiasis mono- and co-infections among Nigerian children.

机构信息

Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany.

Department of Medical Microbiology and Parasitology, Ladoke Akintola University of Technology, Osogbo, Nigeria.

出版信息

Trop Med Int Health. 2018 Jan;23(1):45-52. doi: 10.1111/tmi.13007. Epub 2017 Nov 24.

DOI:10.1111/tmi.13007
PMID:29131459
Abstract

OBJECTIVE

Interleukin-10 (IL-10) is an anti-inflammatory cytokine produced by Th1 cells and macrophages. The rationale of this study was to examine and validate possible contributions of IL-10 promoter polymorphisms in sub-Saharan Africa in children infected with either Plasmodium falciparum or Schistosoma haematobium and in children co-infected with both parasites.

MATERIALS AND METHODS

A total of 309 Nigerian children aged 4-15 years were recruited. The study group consisted of individuals infected either with P. falciparum (n = 76) or S. haematobium (n = 94) in mono-infections, a group of children co-infected with both P. falciparum and S. haematobium (n = 62) and matched healthy controls (n = 77). The IL-10 promoter polymorphisms -1082G/A, -819C/T and -592C/A were genotyped by direct sequencing.

RESULTS

The frequencies of the IL-10 -1082GG genotype, the -1082G allele and haplotype GCC (positions -1082, -819 and -592) were higher in children infected with P. falciparum than in healthy controls, indicating that the -1082GG genotype and the -1082G allele and the GCC haplotype are associated with increased susceptibility to malaria infection (OR = 3.4, 95% CI = 1.2-10.8, P = 0.02; OR = 2.5, 95% CI = 1.1-3.4, P = 0.02; OR = 3.8, 95% CI = 2.0-7.2, P = 0.0001, respectively). Children with the -1082GG genotype had a higher parasitaemia than children with the -1082AA or -1082AG genotypes (P = 0.0017). Haplotype GCC occurred more frequently in children infected with S. haematobium, while haplotype GTA was less frequent than in controls (OR = 2.2, 95% CI = 1.2-4.4, P = 0.017 and OR = 0.1, 95% CI = 0.02-0.5, P = 0.0004, respectively). No differences in the frequencies of IL-10 promoter polymorphisms were observed between children with P. falciparum-S. haematobium co-infections and healthy controls.

CONCLUSION

Although IL-10 promoter polymorphisms are not associated with P. falciparum and S. haematobium co-infection, variant -1082G/A and haplotype GCC are associated with malaria, whereas the IL-10 haplotypes GCC and GTA are associated with schistosomiasis.

摘要

目的

白细胞介素-10(IL-10)是 Th1 细胞和巨噬细胞产生的抗炎细胞因子。本研究的原理是研究和验证撒哈拉以南非洲儿童中 IL-10 启动子多态性在感染疟原虫或埃及血吸虫以及同时感染两种寄生虫中的可能作用。

材料和方法

共招募了 309 名年龄在 4-15 岁的尼日利亚儿童。研究组包括感染疟原虫(n=76)或埃及血吸虫(n=94)的个体,分别为单纯感染,一组同时感染疟原虫和埃及血吸虫的儿童(n=62)和匹配的健康对照组(n=77)。通过直接测序对 IL-10 启动子多态性-1082G/A、-819C/T 和-592C/A 进行基因分型。

结果

与健康对照组相比,感染疟原虫的儿童中 IL-10-1082GG 基因型、-1082G 等位基因和 GCC 单倍型(位置-1082、-819 和-592)的频率更高,表明-1082GG 基因型、-1082G 等位基因和 GCC 单倍型与疟疾感染易感性增加相关(OR=3.4,95%CI=1.2-10.8,P=0.02;OR=2.5,95%CI=1.1-3.4,P=0.02;OR=3.8,95%CI=2.0-7.2,P=0.0001)。与-1082AA 或-1082AG 基因型相比,-1082GG 基因型的儿童寄生虫血症更高(P=0.0017)。携带-1082GG 基因型的儿童更易感染埃及血吸虫,而携带-1082GT 基因型的儿童则较少(OR=2.2,95%CI=1.2-4.4,P=0.017 和 OR=0.1,95%CI=0.02-0.5,P=0.0004)。在感染疟原虫和埃及血吸虫的儿童与健康对照组之间,未观察到 IL-10 启动子多态性的频率存在差异。

结论

虽然 IL-10 启动子多态性与疟原虫和埃及血吸虫的混合感染无关,但变体-1082G/A 和单倍型 GCC 与疟疾有关,而 IL-10 单倍型 GCC 和 GTA 与血吸虫病有关。

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