中文摘要：

目的：了解穿孔素基因（PRF1）多态性在噬血细胞综合征（HLH）患儿中的分布情况，探讨PRF1基因多态性与HLH是否存在易感相关性。方法收集2009年1月至2013年12月确诊为HLH的48例患儿（HLH组）及100名健康体检儿童（对照组）的临床资料，应用聚合酶链反应（PCR）结合直接测序方法对两组患儿的PRF1基因编码区（包括3个外显子和2个内含子）进行基因多态性位点筛查。结果48例HLH患儿中，在PRF1基因编码序列中共发现3个SNP位点，而在非编码序列中共发现7个SNP位点；PRF1基因非编码序列中还有2个SNP位点rs10999426和rs10999427分别仅在5例对照组儿童中发现（5%）；以上12个SNP位点在HLH组和对照组中的基因型及等位基因频率分布差异均无统计学意义（P〉0.05）。连锁不平衡分析提示rs10999426和rs10999427紧密连锁（D=1，r2=1），但上述2个位点构建的A-T单体型在HLH组和对照组中的分布频率差异无统计学意义（P〉0.05）。结论 PRF1基因多态性与HLH发病存在易感相关性的可能性不大；rs10999426和rs10999427存在连锁不平衡关系，其构建的A-T单体型虽仅在对照组中发现，但发生率低，可能不是家族性HLH的保护性因素。

英文摘要：

ObjectiveTo investigate frequency distribution of gene polymorphisms of PRF1 gene in children with hemophagocytic lymphohistiocytosis （HLH）, and to explore whether the possible gene polymorphisms of PRF1 gene confer an increased risk of susceptibility to HLH.MethodsForty-eight children who were diagnosed with HLH between January 2009 and December 2013 （HLH group） and 100 healthy children （control group） were enrolled in this study. The gene polymorphisms in the coding region of PRF1 gene, which consists of three exons and two introns, were genotyped by PCR, followed by direct sequencing.ResultsThree single nucleotide polymorphisms （SNPs） were revealed in the coding sequence of PRF1 in the 48 children with HLH. Seven SNPs were detected in the noncoding sequence. Other two SNPs in the noncoding sequence includingrs10999426 and rs10999427 were detected only in 5 healthy children （5%）. There was no signiifcant difference in allelic frequencies of all the SNPs above between the HLH and control groups （P〉0.05）. Haplotype analysis showed there was a pair-wise linkage disequilibrium between rs10999426 and rs10999427 （D=1,r2=1）, but there was no signiifcant difference in the distribution of A-T haplotype between the HLH and control groups （P〉0.05）.ConclusionsThere is no association between gene polymorphisms of PRF1 gene and the susceptibility to HLH. There is a pair-wise linkage disequilibrium between rs10999426 and rs10999427, but a low detection rate of A-T haplotype in healthy children indicates that it might not play a protective role in the development of HLH.