Kaneshige T, Hashimoto M, Kinoshita T, Moribe T, Inagawa A, Itou Y, Fukunishi T, Teraoka H, Inoko H
Diagnostic Science Department, Shionogi & Co., Ltd., Osaka, Japan.
Tissue Antigens. 1997 Jan;49(1):46-52. doi: 10.1111/j.1399-0039.1997.tb02709.x.
We analyzed the frequencies and haplotypes of DQA103 and 05 subtypes, DQA103011 or DQA10302 and DQA10501 or DQA10503, respectively, differing only at codon 160 in the non-polymorphic third exon of the DQA1 gene. Of these, 1,862 and 337 individuals selected as DQA103- and DQA105-positive samples, respectively among 2,215 unrelated Japanese were typed for their nucleotide variation at residue 160 using PCR-SSP. As observed in other populations, all the samples carrying DQA103011 (Gene Frequency, GF: 7.8%) were found to share DQB10302, whereas those carrying DQA10302 (GF: 44.3%) were associated with a variety of DQB1 alleles including DQB10302. Both of the DQA1-DQB1 haplotypes with DQA103011 and DQA10302 carrying DRB10406, DQA103011-DQB10302 and DQA10302-DQB10302, showed a strong linkage disequilibrium with B62 (p < 0.001, p < 0.05). These results suggested that DQA103011 was generated from a single amino acid change at residue 160 in the DQA10302-DQB10302 haplotype. However, none of the haplotypes with two different DQA103 subtypes carrying DRB10403,0405,0802 and 0901 showed a linkage disequilibrium with any common B-locus antigens, revealing extensive haplotypic diversity of the DQA103 group. For example, DRB10802 haplotypes showed linkage disequilibria with two different B-locus antigens, B35 and B61 depending on the presence of DQA103011 and DQA10302, respectively. The GFs of DQA10501 and 0503 were 5.1% and 2.7%, respectively. The DQA105 associated haplotypes in the DR52-antigen group with DQB10301 were divided into two groups, depending on the bimorphism at residue 160. Such a high degree of haplotypic diversity in association with DRB1 and B alleles observed in the DQA103 and *05 groups related to amino acid variation at residue 160, which may affect biological function such as the interaction between CD4 and HLA-DQ molecules, seems to reflect selective pressure in the evolutionary process of HLA antigens.
我们分析了DQA103和05亚型、分别为DQA103011或DQA10302以及DQA10501或DQA10503的单倍型频率，它们仅在DQA1基因非多态性第三外显子的第160密码子处存在差异。在2215名无亲缘关系的日本人中，分别选取1862名和337名被判定为DQA103和DQA105阳性的样本，使用聚合酶链反应-序列特异性引物（PCR-SSP）对其第160位残基的核苷酸变异进行分型。正如在其他人群中所观察到的，所有携带DQA103011（基因频率，GF：7.8%）的样本均被发现共享DQB10302，而那些携带DQA10302（GF：44.3%）的样本则与包括DQB10302在内的多种DQB1等位基因相关。携带DRB10406的DQA103011和DQA10302的两种DQA1-DQB1单倍型，即DQA103011-DQB10302和DQA10302-DQB10302，与B62呈现出强烈的连锁不平衡（p < 0.001，p < 0.05）。这些结果表明，DQA103011是由DQA10302-DQB10302单倍型第160位残基处的单个氨基酸变化产生的。然而，携带DRB10403、0405、0802和0901的两种不同DQA103亚型的单倍型，均未与任何常见的B位点抗原呈现连锁不平衡，这揭示了DQA1
