CAJ | 학술논문

目的研究中国汉族人群KIR2DLl高分辨等位基因频率及识别HLA-C配体的分布特点.方法采用基因测序和序列特异性引物聚合酶链反应(PCR-SSP)方法,对中华骨髓库登记的111例患者和116名无关供者,共计227份样本进行KIR2DL1高分辨等位基因分型和KIR基因分型,有105例患者接受异基因造血干细胞移植(allo-HSCT).结果 227份样本中有224份(98.68％)样本存在KIR2DL1基因,在448个等位基因中共发现3种KIR2DL1*00302、*00201、*00401等位基因多态性,基因表型频率分别为84.82％ (380/448)、12.05％ (54/448)和3.13％ (14/448),等位基因频率分别为61.04％、6.22％、1.58％,并与欧美人种基因频率分布差异有统计学意义.在6种KIR2DL1高分辨等位基因组合中KIR2DL1*00302、00302(74.55％)纯合组合为最常见的基因型,且KIR2DL1*00302、00401组合频率在A/A和B/x中的分布差异有统计学意义(P=0.001),含KIR2DL1*00401的等位基因组合在A/A中无基因频率分布.KIR2DL1*00302和KIR2DL1*00201分别均与KIR2DS1、KIR2DL3、KIR2DS4和KIR3DL 1/Sl有连锁关系(P＜ 0.001).在allo-HSCT的KIR/HLA受配体模式中KIR2DL1*00302与HLA-C2组位点存在相关性,且与HLA-C*06:02是最常见的识别受配体组合,而与HLA-C*01:02受配体模式是最常见的产生异源反应活性的组合,二者在受配体模式中的分布差异具有统计学意义(P＜0.05).结论 KIR2DL1* 00302是中国汉族人群中最常见的等位基因,KIR2DL1高分辨基因分型可预测移植后供者NK细胞的异源反应活性并有利于供者的筛选.
목적 연구중국한족인군KIR2DLl고분변등위기인빈솔급식별HLA-C배체적분포특점.방법 채용기인측서화서렬특이성인물취합매련반응(PCR-SSP)방법,대중화골수고등기적111례환자화116명무관공자,공계227빈양본진행KIR2DL1고분변등위기인분형화KIR기인분형,유105례환자접수이기인조혈간세포이식(allo-HSCT).결과 227빈양본중유224빈(98.68％)양본존재KIR2DL1기인,재448개등위기인중공발현3충KIR2DL1*00302、*00201、*00401등위기인다태성,기인표형빈솔분별위84.82％ (380/448)、12.05％ (54/448)화3.13％ (14/448),등위기인빈솔분별위61.04％、6.22％、1.58％,병여구미인충기인빈솔분포차이유통계학의의.재6충KIR2DL1고분변등위기인조합중KIR2DL1*00302、00302(74.55％)순합조합위최상견적기인형,차KIR2DL1*00302、00401조합빈솔재A/A화B/x중적분포차이유통계학의의(P=0.001),함KIR2DL1*00401적등위기인조합재A/A중무기인빈솔분포.KIR2DL1*00302화KIR2DL1*00201분별균여KIR2DS1、KIR2DL3、KIR2DS4화KIR3DL 1/Sl유련쇄관계(P＜ 0.001).재allo-HSCT적KIR/HLA수배체모식중KIR2DL1*00302여HLA-C2조위점존재상관성,차여HLA-C*06:02시최상견적식별수배체조합,이여HLA-C*01:02수배체모식시최상견적산생이원반응활성적조합,이자재수배체모식중적분포차이구유통계학의의(P＜0.05).결론 KIR2DL1* 00302시중국한족인군중최상견적등위기인,KIR2DL1고분변기인분형가예측이식후공자NK세포적이원반응활성병유리우공자적사선.
Objective To find out the distributed characteristics of KIR2DL1 alleles frequencies and the recognition HLA-C ligand in the Chinese Han population.Methods The 111 patients and 116 donors from CMDP were performed the KIR2DL1 high-resoluction typing and KIR genotyping using sequence-based testing (SBT) and PCR-SSP methods.Results A total of 224 individuals with KIR2DL 1 locus was predominantly observed and accounted for 98.68％ (224/227).There were 3 different KIR2DL1 alleles,including KIR2DL1*00302,*00201 and *00401 alleles polymorphism.The most common phenotype observed were KIR2DL1*00302 (84.82％,380/448),KIR2DL 1*00201 (12.05％,54/448) and KIR2DL1*00401 (3.13％,14/448),present at allele genetype frequencies of 61.04％,6.22％ and 1.58％respectively.The allele homozygotic types of KIR2DL1*00302 and KIR2DL1*00302 were the most frequent in 6 KIR2DL1 allele by high resolution typing.The allele heterozygous types of KIR2DL1*00302 and KIR2DL 1 * 00401 presented statistically different in haplotypes A/A and B/x (P=0.001),and KIR2DL1 *00401 lacked of all A/A haplotype.The KIR2DL1*00302 and KIR2DL1*00201 allele had significant positive associations between different KIR pairs of KIR2DS1、KIR2DL3、KIR2DS4 and KIR3DL1/S1 using linkage diseduilibrium analysis (P ＜ 0.01),respectively.In the receptor-ligand of KIR/HLA model after al1o-HSCT,KIR2DL1*00302 alleles correlated with their HLA-C2 group ligands.KIR2DL1*00302 and HLA-C*06:02 was the most common combination ligand model,but KIR2DL1*00302 and HLA-C*01:02 was the most frequent mismatch ligand model with the development of NK cell-induced alloreactivity,meanwhile there was statistically significant difference of frequency distribution (P＜ 0.05).Conclusion The KIR2DL1*00302 was the most frequent allele in Chinese Han population.The KIR2DL1 high resolution typing would be beneficial for predicting donor NK cells alloactivity after hematopoietic stem cell transplantation and selecting suitable donors.