title: Apolipoprotein E gene polymorphisms are associated with psoriasis but do not determine disease response to acitretin.
abstract: BACKGROUND
  Psoriasis is associated with abnormal plasma lipid metabolism and a high frequency of cardiovascular events. Increased lipid levels are also seen in patients with psoriasis treated with acitretin. Apolipoprotein E (ApoE) variants have been linked to hypertriglyceridaemia and hypercholesterolaemia in normal individuals. Two coding single nucleotide polymorphisms at +3937 and +4075 define the three common ApoE alleles e2, e3 and e4.
  
  
  OBJECTIVE
  To test the hypothesis that particular ApoE polymorphism(s) are associated with psoriasis and that specific ApoE allelic variant(s) may be a marker for predicting disease response to acitretin.
  
  
  METHODS
  DNA was genotyped for ApoE polymorphisms using a radioactive hybridization technique in cohorts of patients with psoriasis, including patients with chronic plaque psoriasis (CPP, n = 212), guttate psoriasis (GP, n = 94), palmoplantar pustulosis (PPP, n = 101), controls (n = 137), acitretin responders (n =106) and acitretin nonresponders (n = 84).
  
  
  RESULTS
  The frequency of the e4 allele (+3937C/+4075C) was significantly higher in patients with CPP and GP than in controls (P = 0.008 and P = 0.02, respectively). There was no significant difference in allele frequencies between patients with PPP and controls. Allelic distribution was similar in acitretin responders and nonresponders.
  
  
  CONCLUSIONS
  These data demonstrate an association between the Apo e4 allele and CPP and GP, suggesting a possible pathogenic role for ApoE in psoriasis. Our results do not support a link between disease response to acitretin and the e2, e3 or e4 allelic variants of ApoE.
authors.affiliation: The Dermatology Centre, University of Manchester, Hope Hospital, Manchester, UK. emanuela.campalani@kcl.ac.uk
authors.forename: E
authors.initials: E
authors.lastname: Campalani
authors.forename: M H
authors.initials: MH
authors.lastname: Allen
authors.forename: D
authors.initials: D
authors.lastname: Fairhurst
authors.forename: H S
authors.initials: HS
authors.lastname: Young
authors.forename: C O
authors.initials: CO
authors.lastname: Mendonca
authors.forename: A D
authors.initials: AD
authors.lastname: Burden
authors.forename: C E M
authors.initials: CE
authors.lastname: Griffiths
authors.forename: M A
authors.initials: MA
authors.lastname: Crook
authors.forename: J N W N
authors.initials: JN
authors.lastname: Barker
authors.forename: C H
authors.initials: CH
authors.lastname: Smith
mesh_terms: D017255:Acitretin / Q000009:adverse effects / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D002648:Child; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015228:Hypertriglyceridemia / Q000139:chemically induced / Q000235:genetics; D007641:Keratolytic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D011565:Psoriasis / Q000188:drug therapy / Q000235:genetics*; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D005819:Genetic Markers; D007641:Keratolytic Agents; D017255:Acitretin