Promoter analysis of IL-4R gene and its possible associateion of atopic dermatitis

IL-4R基因启动子分析及其与特应性皮炎的可能关系

• 批准号: 13670897
• 负责人: FUKAI Kazuyoshi
• 金额: $ 2.24万
• 依托单位: Osaka City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670897/
• 关键词: ATOPIC DERMATITIS; PSORIASIS; POLYMORPHISM; TRANSCRIPTION FACTOR; PROMOTER; インターロイキン4レセプター; SNP; サイトカイン; 遺伝子発見の調節

The gene encoding the interleukin-4 receptor alpha chain (IL4R) has received attention as a candidate gene for atopic diseases, and associations have been reported between functionally significant coding polymorphisms of the gene and atopic diseases (Khurana et al. 1997; Mitsuyasu et al. 1998; Oiso et al 2000). Recently, Ober et al. (2000) suggested that the variations outside the coding region of the IL4R gene influence the susceptibility for atopy and asthma. Therefore, we investigated the 5'-flanking region of the gene and identified four new polymorphisms in the IL4R transcriptional promoter: -327A/C, -326C/A, -186A/G, -184A/G. We carried out association study of these polymorphisms in patients with 111 cases of atopic dermatitis versus 82 normal controls. We also recruited 73 patients with psoriasis vulgaris as the second control group. We further investigated more upstream of the 5'-flanking region of the gene and identified two new polymorphisms: -1914T/C and -3223C/T. Frequency of these polymorphisms were examined in 118 patients with atopic dermatitis, 89 normal controls and 70 patients with psoriasis. We found that these polymorphisms have association with atopic dermatitis. Unexpectedly, we also found that four polymorphisms; -327A/C, -326C/A, -186A/G, -184A/G have association with psoriasis as well.

编码白介素 4 受体 α 链 (IL4R) 的基因作为特应性疾病的候选基因而受到关注，并且已报道该基因的功能上显着的编码多态性与特应性疾病之间的关联（Khurana 等人，1997 年；Mitsuyasu 等人） 1998；大矶等人，2000）。最近，奥伯等人。 (2000)表明IL4R基因编码区之外的变异影响特应性和哮喘的易感性。因此，我们研究了该基因的5'侧翼区域，并鉴定了IL4R转录启动子中的四个新的多态性：-327A/C、-326C/A、-186A/G、-184A/G。我们对 111 例特应性皮炎患者与 82 例正常对照患者的这些多态性进行了关联研究。我们还招募了 73 名寻常型银屑病患者作为第二个对照组。我们进一步研究了该基因 5' 侧翼区域的更上游，并鉴定了两个新的多态性：-1914T/C 和 -3223C/T。在 118 名特应性皮炎患者、89 名正常对照者和 70 名银屑病患者中检查了这些多态性的频率。我们发现这些多态性与特应性皮炎有关。出乎意料的是，我们还发现了四个多态性； -327A/C、-326C/A、-186A/G、-184A/G 也与牛皮癣有关。

项目成果

A. Kato, K. Fukai, N. Oiso, N. Hosomi, T. Murakami, M. Ishii: "Association of SPINK5 gene polymorphisms with atopic dermatitis in the Japanese population"Br J Dermatol. (in press).

A. Kato、K. Fukai、N. Oiso、N. Hosomi、T. Murakami、M. Ishii：“SPINK5 基因多态性与日本人群特应性皮炎的关联”Br J Dermatol。

A Kato, K Fukai, et al.: "A novel P gene missense mutation in a Japanese"J Delmatol Sci. (in press).

A Kato、K Fukai 等人：“日本人中的一种新型 P 基因错义突变”J Delmatol Sci。

Karim M, Suzuki K, Fukai,K, Oh J, Nagle DL, Moore K, Barbosa E, Falik-Borenstein T, Filipovich A, Ishida Y, Kivrikko S, Klein C, Kreuz F, Levin A, Miyajima H, Russo C, Uyama E, Vierimaa O, Spritz R: "Apparent genotype-phenotype correlation in 'childhood',

Karim M、铃木 K、Fukai、K、Oh J、Nagle DL、Moore K、Barbosa E、Falik-Borenstein T、Filipovich A、Ishida Y、Kivrikko S、Klein C、Kreuz F、Levin A、Miyajima H、Russo C

Karin M, Suzuki K, Fukai K et al.: "Apparent genotype-phenotype correlation in childhood, adolescent, and adult Chediak-Higashi syndrome"Am J Med Genuet. 108(1). 16-22 (2002)

Karin M、Suzuki K、Fukai K 等人：“儿童、青少年和成人 Chediak-Higashi 综合征的明显基因型-表型相关性”Am J Med Genuet。

N Oiso, MD, K Fukai, MD, N Hosomi, MD and M Ishii, MD: "Guttate morphoea with Christmas-tree distribution in a patient with human T-cell lymphoma/lymphotropic virus type-1 (HTLV-1) infection"Clin Exp Dermatol. (in press).

N Oiso, MD、K Fukai, MD、N Hosomi, MD 和 M Ishii, MD：“人类 T 细胞淋巴瘤/嗜淋巴细胞病毒 1 型 (HTLV-1) 感染患者的点状硬斑病与圣诞树分布”