烟台地区汉族人群HLA-Ⅱ类基因区五个基因位点多态性分析

Polymorphism analysis of five HLA classⅡgene loci in Yantai Han population

目的探讨烟台地区汉族人群人类白细胞抗原(human leukocyte antigen,HLA)-DPA1、-DPB1、-DQA1、-DQB1、-DRB1五个位点基因分布多态性及基因型。方法收集2020年6月至2020年12月烟台市中心血站检测合格的汉族无偿献血者外周血样本135例,利用下一代测序(next-generation sequencing,NGS)技术对入组人群进行HLA-DPA1、-DPB1、-DQA1、-DQB1、-DRB1五个位点基因检测和基因型分析,统计分析HLA-DPA1、-DPB1、-DQA1、-DQB1、-DRB1基因频率特点,并与其它地区人群基因分布进行比较。结果在HLA-DRB1、DQA1、DQB1、DPA1、DPB1五个位点检出分布频率最高的等位基因分别是DRB1*09:01、DQA1*01:02、DQB1*03:01、DPA1*02:02、DPB1*05:01;五个位点等位基因中,发现98种HLA-DRB1基因型,频率高于1.48%的有7种;66种HLA-DQB1基因型,频率高于1.48%的有14种;68种HLA-DQA1基因型,频率高于1.48%的有14种;36种HLA-DPB1基因型,频率高于1.48%的有13种;10种HLA-DPA1基因型,频率高于1.48%的有6种。烟台地区汉族人群HLA-DRB1*01:01基因频率明显高于南方汉族人群和沈阳汉族人群(χ^(2)值分别为18.97,7.58,P值均<0.05),-DRB1*07:01、-DRB1*13:01基因频率仅明显高于南方汉族人群(χ^(2)值分别为20.10,12.08;P值均<0.05),而HLA-DRB1*14:54基因频率则明显低于南方汉族人群(χ^(2)=7.76,P<0.05),HLA-DQA1*02:01、-DQA1*05:08、-DQB1*02:02、-DQB1*05:01、-DQB1*06:02、-DQB1*06:03、-DQB1*06:04基因频率明显高于南方汉族人群(χ^(2)值分别为20.93,13.26,12.45,4.95,8.30,10.64,6.53;P值均<0.05),HLA-DQA1*03:03、-DQA1*05:05基因频率明显高于沈阳汉族人群(χ^(2)值分别为13.40,7.50;P值均<0.05),HLA-DQA1*05:03、-DQB1*05:02、-DQB1*06:01则明显低于南方汉族人群(χ^(2)值分别为4.51,13.87,6.43;P值均<0.05),HLA-DPA1*01:03、-DPA1*02:07、-DPB1*02:01、-DPB1*04:02、-DPB1*17:01基因频率明显高于南方汉族人群(χ^(2)值分别为18.34,10.72,254.85,5.11,13.83;P值均<0.05),HLA-DPA1*01:03、-DPB1*05:01基因频率明显高于沈阳汉族人群(χ^(2)值分别为6.54,14.18;P值均<0.05),HLA-DPA1*02:02、-DPA1*04:01、-DPB1*02:02、-DPB1*05:01、-DPB1*13:01、-DPB1*21:01基因频率则明显低于南方汉族人群(χ^(2)值分别为15.41,6.62,6.86,8.20,5.98,29.59;P值均<0.05),其他基因频率与南方及沈阳汉族人群差异无统计学意义(P>0.05)。结论烟台地区汉族人群HLA-Ⅱ类基因区五个位点有其独特的基因频率和基因型分布。

Objective To explore the gene distribution polymorphisms and genotypes of human leukocyte antigen(HLA)-DPA1,-DPB1,-DQA1,-DQB1,-DRB1 in the Han population in Yantai area.Methods A total of 135 peripheral blood samples of Han nationality unpaid blood donors who passed the test from the Yantai city center blood station were collected from June 2020 to December 2020,and Next-Generation Sequencing(NGS)technology were used to perform gene detection and genotype analysis of HLA-DPA1,-DPB1,-DQA1,-DQB1,-DQB1,-DRB1 five loci,and the gene frequency characteristics of HLA-DPA1,-DPB1,-DQA1,-DQB1,-DRB1 were analyzed,and compared the gene distribution with populations in other regions.Results Alleles were detected at HLA-DRB1,DQA1,DQB1,DPA1 and DPB1 loci,among which the most frequent alleles were DRB1*09:01,DQA1*01:02,DQB1*03:01,DPA1*02:02 and DPB1*05:01;Among the five alleles,98 HLA-DRB1 genotypes were found;7 of which had a frequency higher than 1.48%,66 HLA-DQB1 genotypes were found,14 of which had a frequency higher than 1.48%;68 HLA-DQA1 genotypes were found,14 of which had a frequency higher than 1.48%;36 HLA-DPB1 genotypes were found,13 of which had a frequency higher than 1.48%;10 HLA-DPA1 genotypes were found,6 of which had a frequency higher than 1.48%.The HLA-DRB1*01:01 gene frequency in Yantai Han population was significantly higher than that of the southern Han population and the Shenyang Han population(χ^(2) values were 18.97 and 7.58 respectively,both P values<0.05);The gene frequencies of-DRB1*07:01 and-DRB1*13:01 were only significantly higher than those of the southern Han population(χ^(2) values were 20.10 and 12.08;P values were less than 0.05);The HLA-DRB1*14:54 gene frequency was significantly lower than that of the southern Han population(χ^(2) value was 7.76,P value<0.05);The frequencies of HLA-DQA1*02:01,-DQA1*05:08,-DQB1*02:02,-DQB1*05:01,-DQB1*06:02,-DQB1*06:03,-DQB1*06:04 were significantly higher than those of Southern Han population(χ^(2) values were 20.93,13.26,12.45,4.95,8.30,10.64,6.53,all P values<0.05);The frequencies of HLA-DQA1*03:03,-DQA1*05:05 were significantly higher than those of Shenyang Han population(χ^(2) values were 13.40 and 7.50;both P values<0.05);The frequencies of HLA-DQA1*05:03,-DQB1*05:02,-DQB1*06:01 were significantly lower than those of Southern Han population(χ^(2) values were 4.51,13.87,6.43,all P values<0.05);The frequencies of HLA-DPA1*01:03,-DPA1*02:07,-DPB1*02:01,-DPB1*04:02,-DPB1*17:01 were significantly higher than those of Southern Han population(χ^(2) values were 18.34,10.72,254.85,5.11,13.83,all P values<0.05);The frequencies of HLA-DPA1*01:03 and-DPB1*05:01 were significantly higher than those of Shenyang Han population(χ^(2) values were 6.54 and 14.18;both P values<0.05);The frequencies of HLA-DPA1*02:02,-DPA1*04:01,-DPB1*02:02,-DPB1*05:01,-DPB1*13:01,-DPB1*21:01 were significantly lower than those of Southern Han population(χ^(2) values were 15.41,6.62,6.86,8.20,5.98,29.59,all P values<0.05);There was no statistical significance in other gene frequencies between southern and Shenyang Han population(P>0.05).Conclusion The five loci of HLA-Ⅱgene region in Yantai Han population have their unique gene frequency and genotype distribution.