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[白细胞介素-10基因-592(C→A)(rs1800872)单核苷酸多态性与儿童异基因造血干细胞移植后移植物抗宿主病的相关性]

[Association between IL-10 Gene -592(C→A) (rs1800872) SNP and GVHD after Allogeneic Hematopoietic Stem Cell Transplantation in Children].

作者信息

Lin Jia-Yan, Wang Kai, Gao Chao, Liu Shu-Guang, Qin Mao-Quan, Wang Bin, Zhu Guang-Hua, Zheng Hu-Yong

机构信息

Hematology Oncology Center of Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing Key Laboratory of Pediatric Hematology Oncology; National Key Discipline of Pediatrics (Capital Medical University); Key Laboratory of Major Diseases in Children, Ministry of Education; Beijing 100045, China.

Hematology Oncology Center of Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing Key Laboratory of Pediatric Hematology Oncology; National Key Discipline of Pediatrics (Capital Medical University); Key Laboratory of Major Diseases in Children, Ministry of Education; Beijing 100045, ChinaE-mail:

出版信息

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2019 Apr;27(2):573-579. doi: 10.19746/j.cnki.issn.1009-2137.2019.02.043.

DOI:10.19746/j.cnki.issn.1009-2137.2019.02.043
PMID:30998173
Abstract

OBJECTIVE

To study the association between IL-10 gene-592(C→A) (rs1800872) single nucleotide polymorphism (SNP) and the graft versus host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children.

METHODS

Ninety-seven childhood patients and seventy-one donors in the Hematology Oncology Center of Beijing Children's Hospital from Jan 2011 to Jul 2017 were enrolled in this study. The genomic DNA was extracted from peripheral blood cells and the SNP genotype was analyzed using TaqMan SNP genotyping assay.

RESULTS

In malignant patients with AA genotype, the incidence of Ⅱ-Ⅳ grade acute GVHD (aGVHD) was lower than that in patients with AC and CC genotype (9.1% vs 43.5%) (P<0.01), and the gastrointestinal aGVHD rate was also lower (9.1% vs 39.1%) (P<0.05). There's no significant association between patients' genotype and Ⅱ-Ⅳ grade aGVHD in total patients and non-malignant patients. Also, the genotype in patients did not corelate with chronic GVHD (cGVHD) and 1 year transplantation-related mortality (TRM). In cases who received HSCT of donors with AA genotype, the liver aGVHD rate was higher than that in cases who received HSCT of donors with AC and CC genotype (23.1% vs 0.0%) (P<0.05), but the genotype in donors did not correlate with Ⅱ-Ⅳ grade aGVHD, cGVHD and 1 year TRM.

CONCLUSION

AA genotype in the IL-10 gene-592 (C→A) (rs1800872) single nucleotide polymorphism in patients protects pediatric malignant patients against Ⅱ-Ⅳ grade aGVHD and gastrointestinal aGVHD after allo-HSCT. AA genotype in donors is a risk factor for liver aGVHD after allo-HSCT in non-malignant disease.

摘要

目的

研究白细胞介素-10基因-592(C→A)(rs1800872)单核苷酸多态性(SNP)与儿童异基因造血干细胞移植(allo-HSCT)后移植物抗宿主病(GVHD)的相关性。

方法

选取2011年1月至2017年7月在北京儿童医院血液肿瘤中心就诊的97例儿童患者和71例供者纳入本研究。从外周血细胞中提取基因组DNA,采用TaqMan SNP基因分型检测法分析SNP基因型。

结果

AA基因型的恶性疾病患者中,Ⅱ-Ⅳ级急性移植物抗宿主病(aGVHD)的发生率低于AC和CC基因型患者(9.1%对43.5%)(P<0.01),胃肠道aGVHD发生率也较低(9.1%对39.1%)(P<0.05)。在所有患者和非恶性疾病患者中,患者基因型与Ⅱ-Ⅳ级aGVHD之间无显著相关性。此外,患者基因型与慢性移植物抗宿主病(cGVHD)和1年移植相关死亡率(TRM)无关。接受AA基因型供者造血干细胞移植的患者,肝脏aGVHD发生率高于接受AC和CC基因型供者造血干细胞移植的患者(23.1%对0.0%)(P<0.05),但供者基因型与Ⅱ-Ⅳ级aGVHD、cGVHD和1年TRM无关。

结论

患者白细胞介素-10基因-592(C→A)(rs1800872)单核苷酸多态性中的AA基因型可保护儿童恶性疾病患者在allo-HSCT后免受Ⅱ-Ⅳ级aGVHD和胃肠道aGVHD。供者AA基因型是非恶性疾病allo-HSCT后肝脏aGVHD的危险因素。

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