大连地区汉族人群HLA-A,-B,-DRB1位点基因多态性研究

Polymorphisms at HLA-A,-B,-DRB1 loci in Dalian Han population

目的:了解大连地区汉族人群HLA-A,-B,-DRB1位点基因多态性分布特征。方法:采用基因测序及序列特异性寡核苷酸探针的方法对10 000名居住在大连地区健康汉族造血干细胞捐献者进行HLA-A,-B,-DRB1基因分型,从而得到等位基因频率。利用ARLEQUIN软件估算单倍型频率及连锁不平衡参数,使用poptree2软件计算两人群间遗传距离(DA)。结果:大连地区汉族人群中共检出HLA-A基因18个、HLA-B基因32个、HLA-DRB1基因13个,HLA-A*02(31.65%)、B*40(14.84%)、DRB1*15(15.82%)最为常见。三位点单倍型中A*30-B*13-DRB1*07(4.56%)频率最占优势,A*02-B*46-DRB1*09(2.43%)次之。A*30-B*13(6.00%)与B*13-DRB1*07(59.89%)为频率最高的两位点单倍型。A*33-B*58与B*13-DRB1*07为大连地区汉族人群中最强连锁不平衡两位点单倍型,连锁不平衡参数分别为0.336 6和0.665 1。大连汉族人群与国内某些人群进行比较,遗传距离最近的是黑龙江(0.001),其次为吉林(0.002)和山东(0.002),遗传距离最远的是台湾(0.047)。与国外其他人群进行比较,遗传距离最近的是泰国(0.029)和韩国(0.03),而遗传距离最远的是意大利(0.183)。结论:大连地区汉族人群HLA-A,-B,-DRB1基因具有较为丰富的多态性,其分布符合北方人群的特点。

Objective：To investigate the polymorphisms at HLA-A,-B,-DRB1 loci in Dalian Han population.Methods：A total of 10 000 unrelated marrow donors who live in Dalian were genotyped by SBT and SSO methods.Haplotype frequencies and linkage disequilibrium values were calculated by ARLEQUIN software,and DA genetic distances between populations were calculated by poptree2 software.Results：A total of 18 HLA-A alleles,32 HLA-B alleles and 13 HLA-DRB1 alleles were found in Dalian Han population.HLA-A＊ 02（31.65%）,B ＊ 40（14.84%） and DRB1 ＊ 15（15.82%） occurred most frequently.A ＊ 30-B ＊ 13-DRB1 ＊ 07（4.56%） was determined to be the most common three-locus haplotype and the second predominant haplotype was A＊ 02-B＊ 46-DRB1 ＊ 09（2.43%）.A ＊ 30-B ＊ 13（6.00%） and B ＊ 13-DRB1 ＊ 07（59.89%） were the most common two-locus haplotypes.Moreover,A＊ 33-B＊ 58 and B＊ 13-DRB1＊ 07 were strongest haplotypes with the linkage disequilibria values 0.336 6 and0.665 1,respectively.In China,the closest genetic distances were found with Heilongjiang（0.001） followed by Jilin（0.002） and Shandong（0.002）,the furthest was found with Taiwan（0.047）.Compared with other populations worldwide,the closest genetic distances were found with Thailand（0.029） and Korea（0.03）,the furthest was found with Italy（0.183）.Conclusion：Dalian Han population had rich polymorphism at HLA-A,-B,-DRB1 loci,and the distribution of HLA-A,-B and-DRB1 was in line with the characteristics of the northern population.