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HLA-DRB1*0701和DRB1*1401与台湾人群寻常型银屑病的遗传易感性相关。

HLA-DRB1*0701 and DRB1*1401 are associated with genetic susceptibility to psoriasis vulgaris in a Taiwanese population.

作者信息

Jee S H, Tsai T F, Tsai W L, Liaw S H, Chang C H, Hu C Y

机构信息

Department of Dermatology, National Taiwan University College of Medicine, Taipei, Taiwan.

出版信息

Br J Dermatol. 1998 Dec;139(6):978-83. doi: 10.1046/j.1365-2133.1998.02552.x.

Abstract

We analysed the allelic frequencies of class II human leucocyte antigen (HLA)-DRB1, DQA1, DQB1 and DPB1 by polymerase chain reaction/sequence-specific oligonucleotide probe hybridization typing in 76 Taiwanese psoriasis vulgaris (PSV) patients and 238 Taiwanese non-psoriatic controls. The analysis revealed the following: (i) the DRB10701 allele was positively associated with PSV (relative risk, RR = 6.4, corrected P-value, Pc < or = 0.001); (ii) the DRB11401 allele was positively associated with type I PSV (age at onset < 40 years) (RR = 3.5, Pc < or = 0.001); (iii) the DQA10501 allele was negatively associated with PSV (RR = 0.4, Pc < or = 0.001); (iv) there was no significant association of HLA-DP genes with PSV; and (v) there was a strong association of beta-chain phenylalanine at position 37 (Phe 37) and glutamate or glutamine at position 74 (Glu 74/Gln 74) with PSV (RR = 3.5, Pc < or = 0.001 for the association of Phe 37 with PSV: RR = 2.2, Pc < or = 0.001 for the association of Glu 74/Gln 74 with PSV). The positive association between PSV and the DRB10701 allele is consistent with previous reports. The negative association of the DQA10501 allele is reported only in Finland, whereas the positive association between PSV and the DRB11401 allele has never been described before. Trans-racial studies may shed further light on the association of class II HLA alleles or other closely linked genes with the development of PSV. Phe 37 (a large, non-polar amino acid) and Glu 74/Gln 74 (both negatively charged amino acids) were the polymorphic residues in pockets 9 and 4, respectively, of the beta-chain, which may have increased their affinity for the small non-polar amino acids and basic amino acids of the psoriatic antigen peptide, thereby activating the T lymphocytes. This finding may facilitate the identification of a psoriatic antigen.

摘要

我们采用聚合酶链反应/序列特异性寡核苷酸探针杂交分型法,分析了76例台湾寻常型银屑病(PSV)患者及238例台湾非银屑病对照者的Ⅱ类人类白细胞抗原(HLA)-DRB1、DQA1、DQB1和DPB1的等位基因频率。分析结果如下:(i)DRB10701等位基因与PSV呈正相关(相对危险度,RR = 6.4,校正P值,Pc≤0.001);(ii)DRB11401等位基因与Ⅰ型PSV(发病年龄<40岁)呈正相关(RR = 3.5,Pc≤0.001);(iii)DQA10501等位基因与PSV呈负相关(RR = 0.4,Pc≤0.001);(iv)HLA-DP基因与PSV无显著相关性;(v)β链第37位苯丙氨酸(Phe 37)以及第74位谷氨酸或谷氨酰胺(Glu 74/Gln 74)与PSV呈强相关(Phe 37与PSV相关的RR = 3.5,Pc≤0.001;Glu 74/Gln 74与PSV相关的RR = 2.2,Pc≤0.001)。PSV与DRB10701等位基因之间的正相关与既往报道一致。DQA10501等位基因的负相关仅在芬兰有报道,而PSV与DRB11401等位基因之间的正相关此前从未有过描述。跨种族研究可能会进一步阐明Ⅱ类HLA等位基因或其他紧密连锁基因与PSV发病的相关性。Phe 37(一种大的非极性氨基酸)和Glu 74/Gln 74(均为带负电荷的氨基酸)分别是β链9号和4号口袋中的多态性残基,这可能增加了它们对银屑病抗原肽的小非极性氨基酸和碱性氨基酸的亲和力,从而激活T淋巴细胞。这一发现可能有助于银屑病抗原的鉴定。

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