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三个欧洲人群中HLA - B44等位基因频率及单倍型关联

HLA-B44 allele frequencies and haplotypic associations in three European populations.

作者信息

Vidan-Jeras B, Breur-Vriesendorp B, Bohinjec M, Jeannet M, Roosnek E, Tiercy J M

机构信息

Blood Transfusion Centre of Slovenia, Ljubljana, Slovenia.

出版信息

Eur J Immunogenet. 1997 Oct;24(5):335-43. doi: 10.1046/j.1365-2370.1997.d01-106.x.

DOI:10.1046/j.1365-2370.1997.d01-106.x
PMID:9442801
Abstract

HLA-B44 is among the most frequent class I antigens in many populations studied so far. It has been subdivided into seven allelic forms that can only be discriminated by DNA typing. Using a simple PCR/sequence-specific oligonucleotide hybridization procedure, we have analysed the frequency distribution of B44 subtypes in three European populations from Slovenia, the Netherlands, and Switzerland. B4402 and B4403 were by far the predominant alleles, B4404 and 4405 were rare, while B4406 and B4407 were not observed. Interestingly, B4402 and 4403 occurred with different frequencies in the three populations, with B4402 being most frequent in the Swiss (65% vs. 57% in the Dutch, and 46.5% in the Slovenes). Of the 139 individuals studied, 60 HLA-B44 ABDR haplotypes could be determined by family studies. In the respective populations, the linkage disequilibria between B44 and other HLA antigens occurred with different frequencies. A2-B4402 haplotypes were very frequent in the Swiss sample, mostly associated with DRB10101, 0401 and 1301. B4402 was more often linked with non-A2 antigens in the Slovenes (predominantly A24, A28) than in the Swiss and the Dutch. The predominant association of B4403 was with DR7: this haplotype was very frequent in the Swiss (82% of the B4403 haplotypes), while lower frequencies were found in the Dutch (72%) and Slovenian (59%) populations. In the Swiss population, more than half of the B44-DR7 haplotypes were A23-B4403-DR7 (53% of all B4403 haplotypes). This haplotype was significantly less frequent in the Slovenian (6%) and in the Dutch (14%) populations. The second most frequent B4403 haplotype in both the Swiss and Slovenes is the A29-B4403-CW1601-DR7 haplotype (17.6 and 29.4%, respectively). Concomitant with the increased frequency of B4403 in the Slovenes, a higher diversity of non-DR7 B44 haplotypes was observed in this population (41% of all B*4403 haplotypes). HLA-B44 oligotyping analysis allowed us to detect B44-subtype incompatibilities in several AB-sero, DRB1/B3/B5-oligo matched unrelated bone marrow donor/patient combinations. The different frequency distributions of HLA-B44 haplotypes in the three populations analysed in this study argue in favour of local volunteer bone marrow donor recruitment. This might significantly improve the chance of finding a highly matched donor for patients with less frequent A-B-DRB1 haplotypes.

摘要

HLA - B44是迄今为止在许多已研究人群中最常见的I类抗原之一。它已被细分为七种等位基因形式,只能通过DNA分型来区分。使用简单的PCR/序列特异性寡核苷酸杂交程序,我们分析了来自斯洛文尼亚、荷兰和瑞士的三个欧洲人群中B44亚型的频率分布。B4402和B4403是迄今为止的主要等位基因,B4404和4405很少见,而未观察到B4406和B4407。有趣的是,B4402和4403在这三个人群中的出现频率不同,B4402在瑞士人中最常见(65%,荷兰人为57%,斯洛文尼亚人为46.5%)。在研究的139名个体中,通过家系研究确定了60种HLA - B44 ABDR单倍型。在各自的人群中,B44与其他HLA抗原之间的连锁不平衡以不同频率出现。A2 - B4402单倍型在瑞士样本中非常常见,主要与DRB10101、0401和1301相关。与瑞士人和荷兰人相比,B4402在斯洛文尼亚人(主要是A24、A28)中更常与非A2抗原连锁。B4403的主要关联是与DR7:这种单倍型在瑞士人中非常常见(B4403单倍型的82%),而在荷兰人(72%)和斯洛文尼亚人(59%)人群中频率较低。在瑞士人群中,超过一半的B44 - DR7单倍型是A23 - B4403 - DR7(占所有B4403单倍型的53%)。这种单倍型在斯洛文尼亚人(6%)和荷兰人(14%)人群中的频率明显较低。瑞士人和斯洛文尼亚人中第二常见的B4403单倍型是A29 - B4403 - CW1601 - DR7单倍型(分别为17.6%和29.4%)。随着斯洛文尼亚人中B4403频率的增加,在该人群中观察到非DR7 B44单倍型的多样性更高(占所有B*4403单倍型的41%)。HLA - B44寡核苷酸分型分析使我们能够在几个AB血清、DRB1/B3/B5寡核苷酸匹配的无关骨髓供体/患者组合中检测到B44亚型不相容性。本研究分析的三个人群中HLA - B44单倍型的不同频率分布支持本地志愿骨髓供体招募。这可能会显著提高为A - B - DRB1单倍型频率较低的患者找到高度匹配供体的机会。

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