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.

编码白细胞介素-4受体α链（IL 4 R）的基因作为特应性疾病的候选基因受到关注，并且已经报道了该基因的功能上重要的编码多态性与特应性疾病之间的关联（Khurana等，1997; Mitsuyasu等，1998; Oiso等，2000）。最近，Ober等人（2000）提出IL 4 R基因编码区以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，并在IL 4 R转录启动子中鉴定了四个新的多态性：-327 A/C，-326 C/A，-186 A/G，-184 A/G。我们对111例特应性皮炎患者和82名正常对照者进行了这些多态性的关联研究。我们还招募了73例寻常型银屑病患者作为第二对照组。我们进一步研究了该基因5 '侧翼区的上游，发现了两个新的多态性：-1914T/C和-3223C/T。检测了118例特应性皮炎患者、89例正常人和70例银屑病患者的多态性频率。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：-327 A/C，-326 C/A，-186 A/G，-184 A/G也与银屑病相关。

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

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”

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。