Variants of C-C motif chemokine 22 (CCL22) are associated with susceptibility to atopic dermatitis: case-control studies.
Variants of C-C motif chemokine 22 (CCL22) are associated with susceptibility to atopic dermatitis: case-control studies.
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DOI：
10.1371/journal.pone.0026987
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Tamari M
中科院分区：
文献类型：
--
作者：
Hirota T;Saeki H;Tomita K;Tanaka S;Ebe K;Sakashita M;Yamada T;Fujieda S;Miyatake A;Doi S;Enomoto T;Hizawa N;Sakamoto T;Masuko H;Sasaki T;Ebihara T;Amagai M;Esaki H;Takeuchi S;Furue M;Noguchi E;Kamatani N;Nakamura Y;Kubo M;Tamari M
特应性皮炎（AD）是一种由多种遗传和环境因素引起的常见炎症性皮肤病。AD的特点是辅助T型2 （Th2）细胞的局部浸润。近年来的临床研究表明Th2趋化因子CCL22和CCL17在AD的发病机制中起重要作用。为了研究CCL22基因多态性是否影响AD易感性，我们对相关变异进行了关联研究和功能研究。我们首先对CCL22基因进行了重测序，共发现了39个snp。我们在CCL22基因中选择了7个标签snp，并使用两个独立的日本人群（第一群体，916例病例和1032例对照；第二群体，1034例病例和1004例对照）进行了相关性研究。通过反方差法合并相关结果后，我们观察到rs4359426的显著相关性（meta分析，合并P = 9.6×10−6；OR, 0.74; 95% CI, 0.65-0.85）。功能分析显示rs4359426风险等位基因有助于CCL22 mRNA的高表达水平。我们进一步研究了等位基因在核蛋白结合上的差异，通过电泳迁移位移试验。从rs223821的G等位基因衍生的dna -蛋白复合物的信号强度高于A等位基因，与rs4359426处于绝对LD。虽然需要进一步的功能分析，但相关变异可能以功能获得的方式在AD易感性中发挥作用。我们的研究结果为阿尔茨海默病的病因和发病机制提供了新的见解。
Atopic dermatitis (AD) is a common inflammatory skin disease caused by multiple genetic and environmental factors. AD is characterized by the local infiltration of T helper type 2 (Th2) cells. Recent clinical studies have shown important roles of the Th2 chemokines, CCL22 and CCL17 in the pathogenesis of AD. To investigate whether polymorphisms of the CCL22 gene affect the susceptibility to AD, we conducted association studies and functional studies of the related variants. We first resequenced the CCL22 gene and found a total of 39 SNPs. We selected seven tag SNPs in the CCL22 gene, and conducted association studies using two independent Japanese populations (1st population, 916 cases and 1,032 controls; 2nd population 1,034 cases and 1,004 controls). After the association results were combined by inverse variance method, we observed a significant association at rs4359426 (meta-analysis, combined P = 9.6×10−6; OR, 0.74; 95% CI, 0.65–0.85). Functional analysis revealed that the risk allele of rs4359426 contributed to higher expression levels of CCL22 mRNA. We further examined the allelic differences in the binding of nuclear proteins by electrophoretic mobility shift assay. The signal intensity of the DNA-protein complex derived from the G allele of rs223821, which was in absolute LD with rs4359426, was higher than that from the A allele. Although further functional analyses are needed, it is likely that related variants play a role in susceptibility to AD in a gain-of-function manner. Our findings provide a new insight into the etiology and pathogenesis of AD.
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影响因子：
4.6
作者：
Hashimoto, Shinichi;Nakamura, Koichiro;Tamaki, Kunihiko
通讯作者：
Tamaki, Kunihiko
影响因子：
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作者：
Flytlie, Helene Aarslev;Hvid, Malene;Deleuran, Bent
通讯作者：
Deleuran, Bent
影响因子：
14.2
作者：
Hamid, Q;Naseer, T;Leung, DYM
通讯作者：
Leung, DYM
影响因子：
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作者：
Mägi R;Morris AP
通讯作者：
Morris AP
影响因子：
12.4
作者：
Perros, F.;Hoogsteden, H. C.;Hammad, H.
通讯作者：
Hammad, H.