Genetic control of the susceptibility to psoriasis.

牛皮癣易感性的基因控制。

• 批准号: 02670480
• 负责人: MUTO Masahiko
• 金额: $ 1.02万
• 依托单位: Yamaguchi University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02670480/
• 关键词: Psoriatic arthritis; Psoriasis vulgaris; Pustular psotiasis; Disease susceptibility; HLA genes; Anaphylatoxin C4a; Linoleic acid; HLAハプロタイプ; HLA

Psoriasis is considered a multifactorial disease, and its clinical manifestations may well reflect this heterogeneous etiology.In order to elucidate distinct (or universal) haplotypes carrying the susceptibility to psoriasis, we performed serotyping and/or DNA-oligotyping of 154 unrelated Japanese patients with psoriasis. Sixty-two out of the 154 were psoriasis vulgaris (PV), 19 were psoriatic arthritis (PA) and 73 were pustular psoriasis (PP). HLA data on 71 out of the 73 PP patients were cited from a report by A. Ohkawara et al. (1990).1)HLA-Al-B37-Cw6 and B39-Cw7 haplotypes had association with PV.2)HLA-A2-Bw46-Cwll-DRw8-DQw6-DPB2.2 (primary associated HLA antigen was HLA-A2) and B27 had association with PA. By using the method proposed by Thomson and Bodmer, the susceptibility gene in linkage disequilibrium with HLA-A2 seems to be inherited in a dominant fashion.3)There was no difference on DNA polymorphism of HLA-A2 gene between patients with PA and healthy controls, according to RFLP analysis of the HLA-A2 gene.4)HLA-A2 had association with PP.5)HLA-DRw13-DQW6 haplotype frequency was decreased both in PA and in PV.6)No globally universal HLA haplotype was identified as the carrier of susceptibility to psoriasis (PV, PA and PP).A study on biological roles of the HLA haplotypes in psoriasis revealed the following findings :1)HLA-A2-Bw46-Cwll-DRw8-D9. w6-DPB2.2 haplotype-positive PA patients had a correlation with increased serum levels of anaphylatoxin C4a derived from complement component C4.2)HLA-A1-B37-Cw6 haplotype showed association with low serum levels of linoleic acid among patients with PV.Association between HLA class I antigens and class II antigens and psoriasis supports that some part of psoriasis is recognized as a disease with immunogenetic disorders. Further investigations by using transgenic mice introduced particular HLA alleles might be necessary to clarify the pathogenesis of psoriasis.

银屑病被认为是一种多因素的疾病，其临床表现可能很好地反映了这种异质性的病因。为了阐明不同的（或普遍的）单倍型进行银屑病的易感性，我们进行了血清分型和/或DNA寡聚体分型的154无关的日本银屑病患者。154例中62例为寻常型银屑病（PV），19例为银屑病关节炎（PA），73例为脓疱型银屑病（PP）。73例PP患者中71例的HLA资料引自A. 1）HLA-A1-B37-Cw 6和B39-Cw 7单倍型与PV相关。2）HLA-A2-Bw 46-Cw 11-DRw 8-DQw 6-DPB 2.2（主要相关HLA抗原为HLA-A2）和B27与PA相关。根据Thomson和Bodmer提出的方法，与HLA-A2连锁不平衡的易感基因可能以显性方式遗传。3）PA患者与健康对照组的HLA-A2基因多态性无差异，HLA-A2基因的RFLP分析表明，HLA-A2与PP有关联，HLA-DRw 13-DQW 6单倍型频率在PA和PV中均降低尚未发现全球通用的HLA单倍型与银屑病易感性（PV、PA和PP）有关，对HLA单倍型在银屑病中的生物学作用的研究发现：1）HLA-A2-Bw 46-Cw 11-DRw 8-D9。2）HLA-A1-B37-Cw 6单倍型与PV患者血清亚油酸水平降低相关。HLA Ⅰ类抗原和Ⅱ类抗原与银屑病的相关性支持银屑病的某些部分是免疫遗传性疾病。进一步的研究，通过使用转基因小鼠引入特定的HLA等位基因可能是必要的，以澄清银屑病的发病机制。

项目成果

Muto, M., et al.: "Correlation between HLA-A2-Bw46-DRw8 haplotype and increased levels of complement components (C4 and C4a) in patients with psoriatic arthritis." Arch. Dermatol. Res. 283. 347-349 (1991)

Muto, M. 等人：“银屑病关节炎患者的 HLA-A2-Bw46-DRw8 单倍型与补体成分（C4 和 C4a）水平升高之间的相关性。”

Muto, M., et al.: "Immunogenetic analysis of an HLA-linked susceptibility gene to psoriatic arthritis in Japanese." Proceedings of The 7th Korea-Japan Joint Meeting of Dermatology 1991.

Muto, M. 等人：“日本人银屑病关节炎 HLA 相关易感基因的免疫遗传学分析。”

武藤 正彦ほか: "遺伝解析からみた膿疱性乾癬の位置づけ." 日本乾癬学会雑誌.

Masahiko Muto 等人：“从遗传分析的角度看脓疱型银屑病的地位。”日本银屑病协会杂志。

Muto, M., et al: "Generalized pustular psoriasis by genetic analysis with HLA." Jpn. J. Psoriasis Res.

Muto, M., 等人：“通过 HLA 基因分析发现全身性脓疱型银屑病。”

Muto, M., et al: "Analysis of HLA-linked disease susceptibility in development of psoriasis vulgaris and composition of fatty acids in plasma." Jpn. J. Psoriasis Res.

Muto, M. 等人：“寻常型银屑病发生过程中 HLA 相关疾病的易感性分析以及血浆中脂肪酸的组成。”