title: Common FLG mutation K4671X not associated with atopic dermatitis in Han Chinese in a family association study.
abstract: BACKGROUND
  Filaggrin gene (FLG) mutations have been identified as the cause of ichthyosis vulgaris (IV) and major predisposing factors for atopic dermatitis (AD). The relationship among AD, IV and FLG mutations has not been clarified yet. Mutations 3321delA and K4671X, two of the most common mutations in Chinese patients, were both statistically associated with AD in case-control studies.
  
  
  METHODS
  A group of 100 family trios (a total of 300 members with one affected AD proband and both parents) were recruited and screened for three filaggrin null mutations (3222del4, 3321delA and K4671X). The subjects' manifestations of AD and IV were assessed by two experienced dermatologists and recorded in detail. The relationship of common mutations to AD were assessed using both case-control and family-based tests of association. Filaggrin expression was measured in skin of 3 subjects with K4671X heterozygote and the normal control using quantitative real-time RT-PCR and immunohistochemistry.
  
  
  RESULTS
  Of 100 probands for AD, 22 were carriers for common FLG mutations and only 2 of them were from 40 none-IV family trios (5.00%), consistent with that of the healthy control group (3.99%, P>0.05). Significant statistical associations were revealed between AD and 3321delA (P<0.001, odds ratio 12.28, 95% confidence interval 3.35-44.98) as well as K4671X (P = 0.002, odds ratio 4.53, 95% confidence interval 1.77-11.60). The family-based approach revealed that 3321delA was over-transmitted to AD offspring from parents (T:U = 12∶1, P = 0.003) but failed to demonstrate transmission disequilibrium between K4671X and AD (T:U = 10∶8, P = 0.815). Moreover, compared to the normal control, filaggrin expression at both mRNA and protein levels in epidermis of subjects with K4671X(heter) was not reduced.
  
  
  CONCLUSIONS
  AD patients from none-IV family trios have low probability of carrying FLG mutations. The present family samples confirmed the susceptibility of mutation 3321delA to AD in Han Chinese. K4671X was not a pathogenic mutation.
authors.affiliation: Department of Dermatology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Ruhong
authors.initials: R
authors.lastname: Cheng
authors.forename: Ming
authors.initials: M
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Guo
authors.forename: Xilan
authors.initials: X
authors.lastname: Chen
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Tao
authors.forename: Aifang
authors.initials: A
authors.lastname: Jiang
authors.forename: Jiecheng
authors.initials: J
authors.lastname: Gan
authors.forename: Huaishan
authors.initials: H
authors.lastname: Qi
authors.forename: Hong
authors.initials: H
authors.lastname: Yu
authors.forename: Wanqing
authors.initials: W
authors.lastname: Liao
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Yao
mesh_terms: D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution / Q000235:genetics; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002675:Child, Preschool; D002681:China; D003876:Dermatitis, Atopic / Q000235:genetics* / Q000473:pathology; D005006:Ethnicity / Q000235:genetics*; D005190:Family; D005260:Female; D000091344:Filaggrin Proteins; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D016112:Ichthyosis Vulgaris / Q000235:genetics / Q000473:pathology; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins