title: Evidence of an association between desmoglein 3 haplotypes and pemphigus vulgaris.
abstract: BACKGROUND
  Pemphigus vulgaris (PV, OMIM 169610) is a severe blistering disorder of the skin and mucous membranes, caused by the production of autoantibodies directed against the epithelial adhesive protein desmoglein 3. Although an association between PV and HLA class II alleles has been established, the genetic factors predisposing to the disease remain poorly understood, the rarity of PV hampering the recruitment of substantial patient cohorts.
  
  
  OBJECTIVE
  To investigate DSG3 as a candidate PV susceptibility gene.
  
  
  METHODS
  We examined five DSG3 single nucleotide polymorphisms (rs8085532, rs3911655, rs3848485, rs3794925 and rs1466379) in two case-control datasets respectively originating from the U.K. (62 PV patients, 154 controls) and northern India (28 patients, 98 controls).
  
  
  RESULTS
  In the U.K. sample, we observed a significant association between PV and the DSG3*TCCTC haplotype (Fisher's exact test P = 0.002). A related haplotype (DSG3*TCCCC) was associated with PV in the Indian dataset (P = 0.002). We also found that all British and Indian patients bearing DSG3 risk haplotypes carried at least one copy of a PV-associated HLA allele.
  
  
  CONCLUSIONS
  These results suggest that genetic variation of DSG3 may be an additive risk factor predisposing to PV and warrant further investigations of this gene.
authors.affiliation: Department of Genetics and Cardiovascular Sciences, University Hospitals Leicester, Leicester, UK. f.capon@ucl.ac.uk
authors.forename: F
authors.initials: F
authors.lastname: Capon
authors.forename: J
authors.initials: J
authors.lastname: Bharkhada
authors.forename: N E
authors.initials: NE
authors.lastname: Cochrane
authors.forename: N J
authors.initials: NJ
authors.lastname: Mortimer
authors.forename: J F
authors.initials: JF
authors.lastname: Setterfield
authors.forename: S
authors.initials: S
authors.lastname: Reynaert
authors.forename: M M
authors.initials: MM
authors.lastname: Black
authors.forename: R W
authors.initials: RW
authors.lastname: Vaughan
authors.forename: R C
authors.initials: RC
authors.lastname: Trembath
authors.forename: K E
authors.initials: KE
authors.lastname: Harman
mesh_terms: D016022:Case-Control Studies; D051184:Desmoglein 3 / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D010392:Pemphigus / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: C071894:DSG3 protein, human; D051184:Desmoglein 3; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains