title: A functional polymorphism in the SPINK5 gene is associated with asthma in a Chinese Han Population.
abstract: BACKGROUND
  Mutation in SPINK5 causes Netherton syndrome, a rare recessive skin disease that is accompanied by severe atopic manifestations including atopic dermatitis, allergic rhinitis, asthma, high serum IgE and hypereosinophilia. Recently, single nucleotide polymorphism (SNP) of the SPINK5 was shown to be significantly associated with atopy, atopic dermatitis, asthma, and total serum IgE. In order to determine the role of the SPINK5 in the development of asthma, a case-control study including 669 asthma patients and 711 healthy controls in Han Chinese was conducted.
  
  
  METHODS
  Using PCR-RFLP assay, we genotyped one promoter SNP, -206G>A, and four nonsynonymous SNPs, 1103A>G (Asn368Ser), 1156G>A (Asp386Asn), 1258G>A (Glu420Lys), and 2475G>T (Glu825Asp). Also, we analyzed the functional significance of -206G>A using the luciferase reporter assay and electrophoresis mobility shift assay.
  
  
  RESULTS
  we found that the G allele at SNP -206G>A was associated with increased asthma susceptibility in our study population (p = 0.002, odds ratio 1.34, 95% confidence interval 1.11-1.60). There was no significant association between any of four nonsynonymous SNPs and asthma. The A allele at -206G>A has a significantly higher transcriptional activity than the G allele. Electrophoresis mobility shift assay also showed a significantly higher binding efficiency of nuclear protein to the A allele compared with the G allele.
  
  
  CONCLUSIONS
  Our findings indicate that the -206G>A polymorphism in the SPINK5 is associated with asthma susceptibility in a Chinese Han population.
authors.affiliation: Department of Medical Genetics and Key Laboratory for Experimental Teratology of the Ministry of Education, Shandong University School of Medicine, Jinan, Shandong 250012, PR China. liuqiji@sdu.edu.cn
authors.forename: Qiji
authors.initials: Q
authors.lastname: Liu
authors.forename: Yu
authors.initials: Y
authors.lastname: Xia
authors.forename: Wenjing
authors.initials: W
authors.lastname: Zhang
authors.forename: Jisheng
authors.initials: J
authors.lastname: Li
authors.forename: Pin
authors.initials: P
authors.lastname: Wang
authors.forename: Huaichen
authors.initials: H
authors.lastname: Li
authors.forename: Chunhua
authors.initials: C
authors.lastname: Wei
authors.forename: Yaoqin
authors.initials: Y
authors.lastname: Gong
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D050980:GATA Transcription Factors / Q000235:genetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D053491:Proteinase Inhibitory Proteins, Secretory / Q000235:genetics*; D000074163:Serine Peptidase Inhibitor Kazal-Type 5; D055815:Young Adult
chemical_list: D050980:GATA Transcription Factors; D053491:Proteinase Inhibitory Proteins, Secretory; C120650:SPINK5 protein, human; D000074163:Serine Peptidase Inhibitor Kazal-Type 5