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黏膜地址素细胞黏附分子1(MADCAM1)基因单核苷酸多态性对异基因造血干细胞移植结局的潜在影响

Possible impact of MADCAM1 gene single nucleotide polymorphisms to the outcome of allogeneic hematopoietic stem cell transplantation.

作者信息

Ambruzova Zuzana, Mrazek Frantisek, Raida Ludek, Stahelova Anna, Faber Edgar, Indrak Karel, Petrek Martin

机构信息

Laboratory of Immunogenomics and Proteomics, Department of Immunology, Palacky University and University Hospital, Olomouc, Czech Republic.

出版信息

Hum Immunol. 2009 Jun;70(6):457-60. doi: 10.1016/j.humimm.2009.03.008. Epub 2009 Mar 12.

DOI:10.1016/j.humimm.2009.03.008
PMID:19286444
Abstract

Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) contributes to the recruitment of donor T cells into the mucosal tissues of the recipient after allogeneic hematopoietic stem cell transplantation (aHSCT). The aim of our study was to determine whether selected single nucleotide polymorphisms (SNPs) of the MADCAM1 gene are associated with development of serious complications after aHSCT. Three MADCAM1 gene single nucleotide polymorphisms (rs758502 C/T, rs2302217 A/G, rs3745925 G/T) were genotyped by polymerase chain reaction with sequence-specific primers in 87 Czech, HLA-identical donor-recipient aHSCT pairs. MADCAM1 rs2302217 AA homozygous recipients developed chronic GVHD more frequently than patients with other genotypes (65% vs. 34%; p = 0.025). Furthermore, multivariate analysis revealed the MADCAM1 rs2302217 AA genotype in recipient being also an independent factor associated with development of acute GVHD (p = 0.036) and decreased overall survival (p = 0.001). These data suggest that MADCAM1 gene polymorphisms may be associated with the risk of chronic GVHD and may, also, affect mortality related to aHSCT.

摘要

黏膜地址素细胞黏附分子-1(MAdCAM-1)在异基因造血干细胞移植(aHSCT)后有助于供体T细胞募集至受体的黏膜组织。我们研究的目的是确定MADCAM1基因选定的单核苷酸多态性(SNP)是否与aHSCT后严重并发症的发生相关。采用序列特异性引物聚合酶链反应对87对捷克HLA匹配的供体-受体aHSCT配对样本进行MADCAM1基因的3个单核苷酸多态性(rs758502 C/T、rs2302217 A/G、rs3745925 G/T)基因分型。MADCAM1 rs2302217 AA纯合子受体发生慢性移植物抗宿主病(GVHD)的频率高于其他基因型患者(65%对34%;p = 0.025)。此外,多因素分析显示,受体的MADCAM1 rs2302217 AA基因型也是与急性GVHD发生相关的独立因素(p = 0.036),且与总生存率降低相关(p = 0.001)。这些数据表明,MADCAM1基因多态性可能与慢性GVHD风险相关,也可能影响aHSCT相关的死亡率。

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