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Abstract
Stromal cell-derived factor-1 (SDF-1), signaling through CXCR4, is implicated in megakaryopoiesis and platelet production. SDF-1 rs2297630 is a functional polymorphism in linkage disequilibrium with other functional variants in SDF-1. This study aimed to investigate the role of SDF-1 rs2297630 in chronic ITP. The genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism and confirmed by direct sequencing. Immature platelet fraction (IPF) was performed using Sysmex XE-2100. Anti-platelet autoantibodies were assayed by enzyme-linked immunosorbent assay. The main characteristics at diagnosis and the outcome of chronic ITP in 201 Chinese patients were retrospectively reviewed. There was no significant difference in either genotype or allelic distribution between ITP patients and the controls (p = 0.114; p = 0.787). However, both heterozygote (GA) and homozygote minor allele (AA) patients had significantly increased megakaryocyte quantity compared to homozygote genotype (GG) patients at diagnosis (p = 0.011). The mean IPF values of GA and AA genotype patients were higher than those observed in the GG genotype patients when platelet counts ≤50 × 109/L at diagnosis (p = 0.007). Patients with GA and AA genotype showed a higher response rate to standard treatments than patients with GG genotype (p < 0.001). In particular, GA and AA genotype patients had a significantly increased chance of responding to steroids, intravenous immunoglobulin (IVIG), and thrombopoietin analogs (p = 0.007; p = 0.029; p = 0.034, respectively). No significant difference was found between anti-platelet antibodies and genotypes (p = 0.296). In summary, the SDF-1 rs2297630 was associated with platelet production and treatment response in Chinese patients with chronic ITP.
Acknowledgments
Mingen Lyu and Renchi Yang designed the research; Mingen Lyu, Yang Li, Yangting Hao performed research; Tiantian Sun, Huiyuan Li, Wenjie Liu, Cuicui Lyu, Rongfeng Fu, Feng Xue, Xiaofan Liu, and Lei Zhang contributed sample collection and essential reagents or tools; Mingen Lyu and Renchi Yang analyzed data; Mingen Lyu and Renchi Yang wrote the paper.
Declaration of interest
The authors have no conflicts of interest.
Funding
This work was supported in part by grants of National Natural Science Foundation of China (81270581, 81300385, and 81470286), Tianjin Municipal Science and Technology Commission (14JCZDJC35100), Specialized Research Fund for the Doctoral Program of Higher Education (20131106120039).