Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Exp Dermatol. 2010 Dec;19(12):1048-53. doi: 10.1111/j.1600-0625.2010.01142.x.
Clinical studies, including twin studies, support the concept that the risk of atopic dermatitis (AD) may be mediated through skin-specific genes, rather than simply through systemic immune or atopy risk genes. The SPINK5 gene is expressed on epithelial surfaces and may provide protection against other allergenic serine proteases. Mutations in the SPINK5 gene result in Netherton syndrome, a disorder characterised by AD, ichthyosis, and elevated serum IgE levels. We genotyped 21 single nucleotide polymorphisms (SNPs) from the SPINK5 gene for 1090 case-control samples (631 patients with AD and 459 normal controls) and analysed the SNPs and haplotypes in this gene and also searched for gene-gene interactions between SPINK5 and the DEFB1 gene that we previously reported. Six SNPs [rs17718511 (P = 0.026), rs17860502 (P = 0.024), KN0001820 (P = 0.045), rs60978485 (P = 0.007), rs17718737 (P = 0.02), and rs1422985 (P = 0.038)] and the haplotype TAA (rs60978485, rs6892205, rs2303064; P = 0.023) in the SPINK5 gene showed significant different allelic or genotypic distributions between the AD group and the control group. We also found that four SNPs [rs17718511 (P = 0.033), rs17860502 (P = 0.031), rs60978485 (P = 0.005), rs17718737 (P = 0.023)] and the haplotype TAA (P = 0.02) in the SPINK5 gene showed associations with the susceptibility of the allergic type of AD (ADe). In addition to this finding, we speculate that the SNPs from DEFB1 and SPINK5 affect the individual susceptibility to development of ADe in an additive manner. This study provides evidence for a significant interaction between allergens and the SPINK5 gene that may contribute to ADe susceptibility.
临床研究，包括双胞胎研究，支持特应性皮炎（AD）的风险可能通过皮肤特异性基因介导的概念，而不是简单地通过全身免疫或特应性风险基因。丝氨酸蛋白酶抑制剂 5 基因（SPINK5）在表皮表面表达，可能对其他变应原丝氨酸蛋白酶提供保护。SPINK5 基因突变导致 Netherton 综合征，这是一种以 AD、鱼鳞病和血清 IgE 水平升高为特征的疾病。我们对 21 个单核苷酸多态性（SNP）进行了基因分型SPINK5 基因 1090 例病例对照样本（631 例 AD 患者和 459 例正常对照），分析了该基因中的 SNP 和单倍型，并搜索了我们之前报道的 SPINK5 和 DEFB1 基因之间的基因-基因相互作用。6 个 SNP [rs17718511（P = 0.026），rs17860502（P = 0.024），KN0001820（P = 0.045），rs60978485（P = 0.007），rs17718737（P = 0.02），和 rs1422985（P = 0.038）]和 SPINK5 基因中的单倍型 TAA（rs60978485、rs6892205、rs2303064；P = 0.023）在 AD 组和对照组之间表现出显著不同的等位基因或基因型分布。我们还发现，4 个 SNP [rs17718511（P = 0.033），rs17860502（P = 0.031），rs60978485（P = 0.005），rs17718737（P = 0.023）]和 SPINK5 基因中的单倍型 TAA（P = 0.02）与过敏性 AD（ADe）的易感性相关。除了这一发现，我们推测 DEFB1 和 SPINK5 中的 SNP 以累加的方式影响个体对 ADe 发展的易感性。这项研究为过敏原与 SPINK5 基因之间的显著相互作用提供了证据，这可能有助于 ADe 的易感性。
