贵州地区57例遗传性持续性胎儿血红蛋白增高症遗传因素分析

目的探讨遗传性持续性胎儿血红蛋白增高症(HPFH)患者存在的珠蛋白基因突变类型及相关单核苷酸多态性(SNP)位点的基因型,分析HPFH中血红蛋白F(HbF)水平升高的分子机制。方法收集HPFH标本,提取全血基因组DNA,采用Gap-PCR检测常见缺失型HPFH;采用PCR扩增与HbF水平升高相关的SNP位点,Sanger测序进行基因分型检测。结果57份HPFH标本中,缺失型HPFH复合β珠蛋白生成障碍性贫血2份(均为SEA-HPFH/CD17);在非缺失型HPFH标本和对照标本中,rs4671393、rs3817621位点基因型分布比较,差异有统计学意义(P<0.05),rs7482144、rs4527238、rs28384513、rs9399137、rs2072597、rs117351327、rs10128556等SNP位点基因型分布比较,差异无统计学意义(P>0.05)。结论SEA-HPFH/CD17、BCL11A基因rs4671393和KLF1基因rs3817621位点多态性可能是导致HPFH发生的遗传因素之一。

Analysis of genetic factors of 57 cases with hereditary persistence of fetal hemoglobin in Guizhou region

Objective To explore the globin gene mutations and genotypes of involved single nucleotide polymorphisms(SNP)in patients with hereditary persistence of fetal hemoglobin(HPFH),and analyze the molecular mechanisms that lead to the increase of hemoglobin F(HbF)level in HPFH.Methods Blood samples of individuals with HPFH were collected.Genomic DNA was extracted from whole blood samples,then common deletional HPFH genotypes were detected by Gap-PCR.PCR was used to amplify the DNA segments containing SNPs which associated with high level of HbF,and genotype of each SNP was determined by Sanger sequencing.Results Among the 57 cases with HPFH,two cases were identified as deletional HPFH compound withβ-thalassemia(SEA-HPFH/CD17).There were statistically significant differences in genotypes distribution of rs4671393 and rs3817621 between the cases with non-deletional HPFH and control individuals(P<0.05),but there were no significant differences in the genotypes distribution of rs7482144,rs4527238,rs28384513,rs9399137,rs2072597,rs117351327,and rs1012855 between the two groups(P>0.05).Conclusion The gene polymorphisms of SEA-HPFH/CD17,BCL11A rs4671393 and KLF1 rs3817621 may be one of the genetic factors causing HPFH.