Abstract
Immune thrombocytopenia (ITP) is an acquired bleeding disease due to immune-mediated destruction of antilogous platelets and ineffective thrombopoiesis. Although the etiology of ITP remains unknown, genetic variants are thought to predispose individuals to the disease. Several candidate gene analyses have identified several loci that increased ITP susceptibility, but no systematic genetic analysis on a genome-wide scope. To extend the genetic evidence and to identify novel candidates of ITP, we performed a pooling genome-wide association study (GWAS) by IlluminaHumanOmniZhongHua-8 combining pathway analysis in 200 ITP cases and 200 controls from Chinese Han population (CHP). The results revealed that 4 novel loci (rs117503120, rs5998634, rs4483616, and rs16866133) were strongly associated with ITP (P < 1.0 × 10−7). Expect for rs4483616, other three loci were validated by the TaqMan probe genotyping assay (P < 0.05) in another cohort including 250 ITP cases and 250 controls. And rs5998634 T allele was more sensitive to glucocorticoids for ITP patients (χ2 = 7.30, P < 0.05). Moreover, we identified three overrepresented signaling pathways including the neuroactive ligand-receptor interaction, pathways in cancer, and the JAK-STAT pathway, which involved in the etiology of ITP. In conclusion, our results revealed four novel loci and three pathways related to ITP and provided new clues to explore the pathogenesis of ITP.
Highlights
Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by low platelet count [1]
Several susceptible genes of ITP have been identified by traditional candidate gene approaches including direct sequencing and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), but these mutations only explain a small fraction of ITP risk
The genetic factor plays a nonnegligible role in modulating the course of ITP
Summary
Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by low platelet count [1]. The incidence of adult ITP is about 5–10 cases/100,000 population annually in China [2]. The etiology of ITP is unclear and is considered multifactorial and polygenic in most cases. The research suggested genetic factor plays an important role in the pathogenesis of ITP [3]. Several susceptible genes of ITP have been identified by traditional candidate gene approaches including direct sequencing and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), but these mutations only explain a small fraction of ITP risk. The majority of heritability for ITP remains to be further elucidated
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