Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Gangnam-Gu, Seoul 135-710, South Korea.
J Dermatol Sci. 2010 Mar;57(3):199-206. doi: 10.1016/j.jdermsci.2009.12.003. Epub 2010 Jan 8.
The acute skin lesions of atopic dermatitis (AD) are associated with Th2 cells; however, the chronic skin lesions of AD are associated with Th1 cells via the action of IL-12.
We evaluated the associations of single nucleotide polymorphisms (SNPs) and haplotype in the IL-12 and IL-12 receptor genes, and determined the gene-gene interactions between the SNPs of these genes and the SNPs of the IL-18 gene that we previously reported.
We genotyped 24 SNPs from 4 IL-12/IL-12R genes for 1089 case-control samples (631 AD patients and 458 normal controls). We measured the serum IL-12 concentrations in 89 individuals (79 AD patients and 10 controls) by ELISA. We analyzed the SNPs and haplotypes in each gene and also searched for the gene-gene interactions.
The rs582504 (IVS-798A/T) SNP and the haplotype TA (rs582054 and rs2243151) in the IL-12A gene, and the rs438421 (IVS12+1266T/C) SNP and the haplotype CCA (rs375947, rs438421, and rs1870063) in the IL-12RB1 gene were significantly associated with the AD phenotype. We showed that the rs438421 polymorphism in the IL-12RB1 (TT) gene and the rs2066446 polymorphism in the IL-12RB2 (AA) gene had a significant interaction to develop the ADe phenotype (allergic type of AD), and those individuals with the risk alleles, TT/AA/CC (IL-12RB1/IL-12RB2/IL-18), have more than a 10-fold increased risk to develop ADe.
This study provides evidence for a significant interaction between the IL-12RB1 and IL-12RB2 genes that contribute to a 4-fold increased risk for developing ADe. In addition to the IL-12R interaction, we suggest that the IL-18 gene can significantly interact with the IL-12R gene to develop ADe. In addition to the interaction, the SNPs and haplotypes in the IL-12A and IL-12RB1 genes are independently and significantly associated with the AD phenotype, and especially with the ADe phenotype. This data may contribute to our understanding of AD genetic interactions and account for the additional risk of certain patients to develop AD.
特应性皮炎（AD）的急性皮肤损伤与 Th2 细胞有关；然而，AD 的慢性皮肤损伤通过 IL-12 的作用与 Th1 细胞有关。
我们评估了 IL-12 和 IL-12 受体基因中单核苷酸多态性（SNP）和单倍型的相关性，并确定了我们之前报道的这些基因的 SNP 与 IL-18 基因的 SNP 之间的基因-基因相互作用。
我们对来自 4 个 IL-12/IL-12R 基因的 24 个 SNP 对 1089 例病例对照样本（631 例 AD 患者和 458 例正常对照）进行了基因分型。我们通过 ELISA 测量了 89 名个体（79 名 AD 患者和 10 名对照）的血清 IL-12 浓度。我们分析了每个基因中的 SNP 和单倍型，并搜索了基因-基因相互作用。
IL-12A 基因中的 rs582504（IVS-798A/T）SNP 和 TA 单倍型（rs582054 和 rs2243151），以及 IL-12RB1 基因中的 rs438421（IVS12+1266T/C）SNP 和 CCA 单倍型（rs375947、rs438421 和 rs1870063）与 AD 表型显著相关。我们表明，IL-12RB1 基因中的 rs438421 多态性（TT）和 IL-12RB2 基因中的 rs2066446 多态性（AA）对 ADe 表型（特应性 AD）的发生具有显著的相互作用，并且携带风险等位基因 TT/AA/CC（IL-12RB1/IL-12RB2/IL-18）的个体发生 ADe 的风险增加了 10 倍以上。
本研究为 IL-12RB1 和 IL-12RB2 基因之间的显著相互作用提供了证据，这导致 ADe 发生的风险增加了 4 倍。除了 IL-12R 相互作用外，我们还提出 IL-18 基因可以与 IL-12R 基因显著相互作用以发生 ADe。除了相互作用外，IL-12A 和 IL-12RB1 基因中的 SNP 和单倍型与 AD 表型独立且显著相关，尤其是与 ADe 表型相关。这些数据可能有助于我们理解 AD 的遗传相互作用，并解释某些患者发生 AD 的额外风险。
