Identification of disease susceptibility genes controlling psoriasis.

本研究的目的是确定控制银屑病的疾病易感基因。通过对100例无血缘关系的日本银屑病患者进行染色体6p21.3上人类主要组织相容性复合体基因(人类白细胞抗原、人绒毛膜促性腺激素受体、肿瘤坏死因子-α)的研究。可以想象，这三个基因可能参与银屑病的发生发展。此外，我们还检测了人类白细胞抗原受体染色体19q上KIR基因的遗传多态性。我们发现以下事实：第一，KIR基因多态性与银屑病的疾病易感性相关。(J.Invest.Dermatol，122：1133-1136,2004)。在外显子4(36 8*C→T，4 0 4*C→T)、外显子14(180 2*G→T)和外显子18(2 40 6*C→G)上观察到Hcr基因的遗传多态性。第三，在人类白细胞抗原、肿瘤坏死因子-α和肿瘤坏死因子-α之间，我们没有发现显著的3种等位基因组合，但我们发现了显著的等位基因组合。此外，作为治疗银屑病的药物之一，对环孢素的反应与KIR基因的多态性有关，因此，人类白细胞抗原-C基因可能是控制银屑病易感性的基因之一。

The aim of the present study was to identify disease susceptibility genes controlling psoriasis. By using unrelated 100 Japanese patients with psoriasis, we investigated the genes (HLA,HCR,TNF-α) within the human major histocompatibility complex on chromosome 6p 21.3. It is conceivable that these three genes can be involved in the development of psoriasis.Furthermore, we examined genetic polymorphisms of KIR on chromosome 19q which is a receptor for HLA. We found the following facts : First, genetic polymorphisms of KIR were associated with the disease susceptibility to psoriasis. (J.Invest.Dermatol.,122:1133-1136,2004). Second, genetic polymorphism of HCR was (α-helix coiled-coil rod homolog) observed at 4 sites (exon4(368*C→T, 404*C→T), exon14(1802*G→T), and exon18(2406*C→G). Third, among HLA,HCR, and TNF-α, we found no significant 3 allelic combinations of HLA-HCR - TNF-α, although we found a significant combination between HLA-Cw6 and HCRs. Furthermore responsive to cyclosporine as one of the psoriatic therapy was associated with KIR polymorphisms.In conclusion, it is possible that HLA-C is one of the hey genes controlling the disease susceptibility to psoriasis.