摘要
目的:探讨全血献血者铁代谢相关基因多态性与铁储备水平的相关性。方法:采用酶联免疫吸附试验(ELISA)检测江苏地区合格献血者血清铁蛋白(SF)浓度,根据SF浓度将所有受检者按照SF<10 ng/mL铁缺乏、10<SF<30 ng/mL铁不足、30<SF<300 ng/mL铁正常、SF>300 ng/mL铁过载分为4组,并提取全血基因组DNA,用PCR方法扩增HFE、GDF15和TMPRSS6基因,利用基因测序对多态性位点进行分型,统计分析基因频率和基因型频率。结果:前期试验对46例SF浓度>300 ng/mL献血者进行基因测序发现HFE rs2071303表现出多态性,其中正常基因型T/T占10.9%(5例),C/T杂合突变占36.9%(17例),C/C纯合突变占52.2%(24例),基因频率及基因型频率均符合Hardy-weinberg平衡定律(P>0.05);另检出5例H63D突变杂合子,占10.9%,其余全为正常基因型。在所有受检者中,TMPRSS6 17号外显子检出4个SNPs位点,TMPRSS6 18号外显子仅检出2个位点且各有1例杂合突变,各位点基因频率及基因型频率均符合Hardy-weinberg平衡定律(P>0.05)。GDF15检出2个SNPs位点,基因频率及基因型频率均符合Hardy-weinberg平衡定律(P>0.05);在GDF15基因上还分别检出4个位点上的4例杂合突变。以上所有位点在性别、SF浓度分布上均差异无统计学意义(P>0.05)。结论:江苏地区全血献血者HFE、GDF15和TMPRSS6基因均具有多态性。H63D突变和rs2071303突变位点与铁过载有相关性值得继续研究,而GDF15和TMPRSS6的基因多态性如何影响献血者铁储备水平还需扩大样本量进一步探讨。
Objective:To explore the correlation between polymorphism of iron metabolism-related gene and iron stores in whole blood donors. Method:The serum ferritin concentration of whole blood donors in Jiangsu area were detected by ELISA method,all subjects were divided into four groups according to SF concentration:SF<10 ng/mL(Iron deficiency),10<SF<30 ng/mL(depleted iron store),30<SF<300 ng/mL(Iron normal),SF>300 ng/mL(Iron overload).The genomic DNA was extracted according to the concentration value.HFE,GDF15 and TMPRSS6 gene were amplified by PCR method,polymorphism sites were classified by gene sequencing,and gene frequencies and genotype frequencies were statistically analyzed. Result:Sequencing 46 blood donors with SF concentration greater than 300 ng/mL,the normal genotype T/T accounted for 10.9%(5 cases),C/T heterozygous mutation accounted for 36.9%(17 cases),and C/C homozygous mutation accounted for 52.2%(24 cases)in the 5 ’end of intron 2 of HFE gene(rs2071303).Gene frequency and genotype frequency were in line with Hardy-Weinberg equilibrium(P>0.05).In addition,5 cases of H63 D mutant heterozygotes were detected,accounting for 10.9%,and the rest were all normal genotypes.Among all the subjects,4 SNPs sites were detected on exon 17 of TMPRSS6 gene and only 2 heterozygous mutations were detected at 2 sites on exon 18 of TMPRSS6 gene,2 SNPs sites on GDF15 gene,and the gene frequency and genotype frequency were in line with Hardy-Weinberg equilibrium(P>0.05).Besides,4 heterozygous mutations were detected at 4 sites on GDF15 gene.There was no statistical difference in gender and SF concentration distribution of the above sites(P>0.05).Conclusion:There are polymorphisms of HFE,GDF15 and TMPRSS6 genes in whole blood donors in Jiangsu area.The correlation between H63 D and rs2071303 and iron overloading may be worthy of further study.However,how the genetic polymorphisms of GDF15 and TMPRSS6 affect the iron stores of blood donors needs to be further discussed by expanding the sample size.
作者
邵雷
王金花
林红
SHAO Lei;WANG Jinhua;LIN Hong(Jiangsu Province Blood Center,Nanjing,210042,China)
出处
《临床血液学杂志（输血与检验）》
CAS
2020年第4期557-562,共6页
Journal of Clinical Hematology(Blood Transfusion & Laboratory Medicine)
基金
江苏省卫健委“六个一工程”项目(No:LGY2016045)。
关键词
全血献血者
铁代谢相关基因
血清铁蛋白
基因频率
基因型频率
whole blood donors
iron metabolism-related gene
serum ferritin
gene frequency
genotype frequency
作者简介
通信作者:林红,E-mail:linhong712003@sina.com。
