The severity of FIP1L1-PDGFRA-positive chronic eosinophilic leukaemia is associated with polymorphic variation at the IL5RA locus
The severity of FIP1L1-PDGFRA-positive chronic eosinophilic leukaemia is associated with polymorphic variation at the IL5RA locus
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DOI：
10.1038/sj.leu.2404977
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发表时间：
2007-12-01
期刊：
影响因子：
11.4
通讯作者：
Cross, N. C. P.
中科院分区：
文献类型：
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作者：
Burgstaller, S.;Kreil, S.;Cross, N. C. P.
我们研究了一种假设，即IL-5信号的体质遗传变异可能与人类FIP1L1-PDGFRA阳性慢性嗜酸性粒细胞白血病(CEL)的发展或严重程度有关。我们对82例FIP1L1-PDGFRA阳性CEL+患者、100例健康人、100例FIP1L1-PDGFRA阴性嗜酸性粒细胞增多症患者和100例慢性粒细胞白血病患者的IL5RA或IL5基因内或附近的6个单核苷酸多态(SNP)进行了基因分型。我们没有发现FIP1L1-PDGFRA阳性病例和对照病例之间的SNP等位基因频率之间存在关联。然而，在FIP1L1-PDGFRA病例中，我们发现IL5RA基因rs4054760和5‘-UTRSNP与外周血嗜酸粒细胞计数(P=0.026)和有无组织浸润有关(P=0.032)。尽管这些关联在多次检测校正后低于显著水平，但在FIP1L1-PDGFRA阴性病例中没有看到这种关联，在整个欧洲的对照人群中也没有发现rs4054760等位基因频率的差异。此外，在对112例CML患者的分析中，IL5RA的表达与rs4054760基因型密切相关(P
We have investigated the hypothesis that constitutional genetic variation in IL-5 signalling may be associated with the development or severity of FIP1L1-PDGFRA-positive chronic eosinophilic leukaemia (CEL) in humans. We genotyped six single-nucleotide polymorphisms (SNP) within or close to the IL5RA or IL5 genes in 82 patients with FIP1L1-PDGFRA-positive CEL plus, as controls, healthy individuals (n=100), patients with FIP1L1-PDGFRA-negative eosinophilia (n=100) or patients with chronic myeloid leukaemia (CML) (n=100). We found no association between SNP allele frequency between FIP1L1-PDGFRA-positive and control cases. However, for FIP1L1-PDGFRA cases, we found an association between the genotype at rs4054760, an SNP in the 5'-UTR of IL5RA and peripheral blood eosinophil count (P=0.026) as well as the presence or absence of tissue infiltration (P=0.032). Although these associations fell below the level of significance once corrected for multiple testing, no such association was seen in FIP1L1-PDGFRA-negative cases and no difference in allele frequencies for rs4054760 was seen in control populations across Europe. Furthermore, in an analysis of 112 patients with CML, IL5RA expression was strongly related to rs4054760 genotype (P