Apolipoprotein E gene polymorphisms are associated with psoriasis but do not determine disease response to acitretin

被引:75
作者
Campalani, E [1 ]
Allen, MH
Fairhurst, D
Young, HS
Mendonca, CO
Burden, AD
Griffiths, CEM
Crook, MA
Barker, JNWN
Smith, CH
机构
[1] St Thomas Hosp, St Johns Inst Dermatol, Skin Therapy Res Unit, London SE1 7EH, England
[2] Univ Manchester, Hope Hosp, Dermatol Ctr, Manchester, Lancs, England
[3] Univ Glasgow, Western Infirm, Dept Dermatol, Glasgow G11 6NT, Lanark, Scotland
[4] Univ Hosp Lewisham, Dept Clin Biochem, London, England
关键词
acitretin; apolipoprotein E; pharmacogenetics; polymorphisms; psoriasis;
D O I
10.1111/j.1365-2133.2005.06950.x
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
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. Objectives 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.
引用
收藏
页码:345 / 352
页数:8
相关论文
共 43 条
[1]   PSORIASIS IN JAPAN [J].
AOKI, T ;
YOSHIKAWA, K .
ARCHIVES OF DERMATOLOGY, 1971, 104 (03) :328-+
[2]   The genetics of psoriasis, psoriatic arthritis and atopic dermatitis [J].
Bowcock, AM ;
Cookson, WOCM .
HUMAN MOLECULAR GENETICS, 2004, 13 :R43-R55
[3]   Apolipoprotein E polymorphism in middle-aged Belgian men: Phenotype distribution and relation to serum lipids and lipoproteins [J].
Braeckman, L ;
DeBacquer, D ;
Rosseneu, M ;
DeBacker, G .
ATHEROSCLEROSIS, 1996, 120 (1-2) :67-73
[4]   MODULATION OF HUMAN-LYMPHOCYTE RESPONSES BY LOW-DENSITY LIPOPROTEINS (LDL) - ENHANCEMENT BUT NOT IMMUNOSUPPRESSION IS MEDIATED BY LDL RECEPTORS [J].
CUTHBERT, JA ;
LIPSKY, PE .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1984, 81 (14) :4539-4543
[5]  
CUTHBERT JA, 1987, INT J TISSUE REACT, V9, P447
[6]  
de Bont N, 2000, EUR J CLIN INVEST, V30, P818
[7]  
Elder JT, 2001, ARCH DERMATOL, V137, P1447
[8]  
ENA P, 1985, ACTA CARDIOL, V40, P199
[9]  
FERRETTI G, 1994, ACTA DERM-VENEREOL, V74, P171
[10]   Apolipoprotein E variation at the sequence haplotype level:: Implications for the origin and maintenance of a major human polymorphism [J].
Fullerton, SM ;
Clark, AG ;
Weiss, KM ;
Nickerson, DA ;
Taylor, SL ;
Stengård, JH ;
Salomaa, V ;
Vartiainen, E ;
Perola, M ;
Boerwinkle, E ;
Sing, CF .
AMERICAN JOURNAL OF HUMAN GENETICS, 2000, 67 (04) :881-900