LNK基因在原发性血小板增多症中的变异及临床意义

Variation and Clinical Significance of LNK Gene in Essential Thrombocytosis

目的:探讨原发性血小板增多症(essential thrombocytosis,ET)中LNK基因的突变及单核苷酸多态性(SNP),并分析其与ET发病的关系。方法:用位点特异性PCR的方法检测JAK2V617F基因突变。用PCR扩增LNK基因外显子全长,扩增序列中包括LNK基因内影响氨基酸表达的Rs3184504(C/T)和Rs78894077(A/C/G/T)以及对氨基酸表达无影响的Rs7973120(A/T)3个SNP位点。测序分析LNK基因突变及单核苷酸多态性。结果:发现6例患者有LNK突变,包括4种类型,分别为A300V、R425C、V402L及R426Q。ET患者SNP Rs78894077Ser(丝氨酸)型T等位基因分布高于正常对照组,差异有统计学意义(P<0.05)。ET患者SNP Rs3184504 Ser(丝氨酸)型T等位基因频率高于正常对照组,差异有统计学意义(P<0.05)。结论:在ET患者中存在LNK基因突变,携带LNK SNP Rs78894077 Ser及Rs3184504 Ser位点T等位基因可增加患ET的风险。

Objective： To explore the mutation and single nucleotide polymorphism（ SNP） of LNK gene in the patients with essential thrombocytosis（ ET）,and to analyze the relationship between LNK gene variation and the occurrence of ET. Methods： JAK2 V617 F mutation was identified by allele-specific PCR. The whole exon of LNK gene was amplified by PCR. The amplified sequences included the Rs3184504（ C/T） and Rs78894077（ A/C/G/T）affecting the expression of amino acids in LNK gene,and the Rs7973120（ A/T） unaffecting the expression of amino acids. The mutation and SNP of LNK gene were analyzed by DNA sequencing. Results： Six cases of ET had LNK mutation,including four types： A300 V,R425 C,V402 L and R426 Q. T allele distribution of SNP Rs78894077 Ser in ET group was statistically significantly higher than that in the control group（ P〈0. 05）. T allele frequency of SNP Rs3184504 Ser in ET group was higher than that in the control group（ P〈0. 05）. Conclusion： LNK mutations exist in ET patients,and the T allele gene carrying LNK SNP Rs78894077 Ser and Rs3184504 Ser in persons may increase the risk of ET.