title: Hint for association of single nucleotide polymorphisms and haplotype in SPINK5 gene with atopic dermatitis in Koreans.
abstract: 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.
authors.affiliation: Case Western Reserve University School of Medicine, Cleveland, OH, USA.
authors.forename: Jung-Hyun
authors.initials: JH
authors.lastname: Namkung
authors.forename: Jong-Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Eugene
authors.initials: E
authors.lastname: Kim
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Byun
authors.forename: Sook
authors.initials: S
authors.lastname: Kim
authors.forename: Eun-Soon
authors.initials: ES
authors.lastname: Shin
authors.forename: Eun-Young
authors.initials: EY
authors.lastname: Cho
authors.forename: Jun-Mo
authors.initials: JM
authors.lastname: Yang
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003876:Dermatitis, Atopic / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D047150:Eosinophil Cationic Protein / Q000097:blood; D004804:Eosinophils / Q000473:pathology; D004843:Epistasis, Genetic / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007723:Korea / Q000208:ethnology; D007958:Leukocyte Count; D008297:Male; D058011:Multifactor Dimensionality Reduction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D053491:Proteinase Inhibitory Proteins, Secretory / Q000235:genetics*; D000074163:Serine Peptidase Inhibitor Kazal-Type 5; D055815:Young Adult; D023083:beta-Defensins / Q000235:genetics
chemical_list: C406407:DEFB1 protein, human; D053491:Proteinase Inhibitory Proteins, Secretory; C120650:SPINK5 protein, human; D000074163:Serine Peptidase Inhibitor Kazal-Type 5; D023083:beta-Defensins; D007073:Immunoglobulin E; D047150:Eosinophil Cationic Protein; C479220:RNASE3 protein, human